lncRNA LINC00460 Research Articles

Effect of Pterostilbene on Regulating LncRNA-Linc00511 Targeting MiR-184 to Promote the Proliferation and Invasion of Non-Small Cell Lung Cancer Under Hypoxic Environment

Non-small cell lung cancer (NSCLC) is one of the most common lung cancers, accounting for more than 85% of lung cancer incidence rates and seriously endangering human health. Increasing evidence shows that some long non-coding RNAs (lncRNAs) act as tumor suppressors and some promote cancer. Pterostilbene-regulated lncRNA-linc00511 has been confirmed to be an oncogenic gene in a variety of tumors. This study aimed to determine the biological function of pterostilbene-regulated lncRNA-linc00511 (LINC00511) in non-small cell lung cancer and provide new diagnostic and therapeutic targets for it. Lung cancer A549 cells were randomly divided into control group and hypoxic group. siRNA knockdown and LINC00511 overexpression plasmid were constructed under hypoxic conditions. Pterostilbene was used to intervene with lncRNA-linc00511. Real time PCR was used to detect the expression changes of LINC00511 and MiR-184. Analyze and detect the effect on the proliferation and invasion of non-small cell lung cancer cells under hypoxic conditions. Real time PCR analysis was used to detect the expression changes of EMT molecules E-cadherin and Vimentin. Western blot detected changes in HIF-1α expression. The expression of LINC00511 increased and the expression of MiR-184 decreased in lung cancer A549 cells, and hypoxic environment led to more significant changes in both. After siRNA knocked down the expression of LINC00511 under hypoxic conditions, pterostilbene was used to intervene with lncRNA-linc00511. The results showed that it promoted the expression of MiR-184, inhibited the proliferation and invasion of lung cancer cells, upregulated the expression of EMT molecules E-cadherin, and increased the expression of Vimentin. The expression is reduced and the expression of HIF-1α is downregulated. Overexpression of LINC00511 can reverse the above changes. Under hypoxic conditions, pterostilbene was used to interfere with lncRNA-linc00511 to promote cell proliferation in non-small cell lung cancer cells. Pterostilbene’s intervention with lncRNA-linc00511 could target the expression of MiR-184 to promote the proliferation and invasion of non-small cell lung cancer. Knocking down the expression of LINC00511 can target down-regulate the expression of MiR-184, change the occurrence of EMT, and alleviate the occurrence and progression of non-small cell lung cancer.

The emerging roles of LINC00511 in breast cancer development and therapy.

Breast cancer (BC) is associated with malignant tumors in women worldwide with persistently high incidence and mortality rates. The traditional therapies including surgery, chemotherapy, radiotherapy and targeted therapy have certain therapeutic effects on BC patients, but acquired drug resistance can lead to tumor recurrence and metastasis. This remains a clinical challenge that is difficult to solve during treatment. Therefore, continued research is needed to identify effective targets and treatment methods, to ultimately implement personalized treatment strategies. Several studies have implicated that the long non-coding RNA LINC00511 is closely linked to the occurrence, development and drug resistance of BC. Here we will review the structure and the mechanisms of action of lnc RNA LINC00511 in various cancers, and then explore its expression and its related regulatory mechanisms during BC. In addition, we will discuss the biological functions and the potential clinical applications of LINC00511 in BC.

Noncoding Ribonucleic Acids (RNAs) May Improve Response to Immunotherapy in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is the seventh most common cause of cancer-related mortality. Despite different methods of treatment, nearly more than 90% of patients with PDAC die shortly after diagnosis. Contrary to promising results in other cancers, immune checkpoint inhibitors (ICIs) showed limited success in PDAC. Recent studies have shown that noncoding RNAs (ncRNAs) are extensively involved in PDAC cell-immune cell interaction and mediate immune evasion in this vicious cancer. PDAC cells recruit numerous ncRNAs to widely affect the phenotype and function of immune cells through various mechanisms. For instance, PDAC cells upregulate miR-301a and downregulate miR-340 to induce M2 polarization of macrophages or overexpress miR-203, miR-146a, and miR-212-3p to downregulate toll-like receptor 4 (TLR4), CD80, CD86, CD1a, major histocompatibility complex (MHC) II, and CD83, thereby evading recognition by dendritic cells. By downregulating miR-4299 and miR-153, PDAC cells can decrease the expression of NK group 2D (NKG2D) and MHC class I chain-related molecules A and B (MICA/B) to blunt the natural killer (NK) cell response. PDAC cells also highly express lncRNA AL137789.1, hsa_circ_0046523, lncRNA LINC00460, and miR-155-5p to upregulate immune checkpoint proteins and escape T cell cytotoxicity. On the other hand, ncRNAs derived from suppressive immune cells promote proliferation, invasion, and drug resistance in PDAC cells. ncRNAs can be applied to overcome resistance to ICIs, monitor the immune microenvironment of PDAC, and predict response to ICIs. This Review article comprehensively discusses recent findings regarding the roles of ncRNAs in the immune evasion of PDAC.

Retraction Note.

The publisher and Editor in Chief have withdrawn four articles published between 2016 and 2018. These articles were discovered to contain problems, such as image manipulation, absence of ethics approval, and inconsistencies in data presented. This retraction notice pertains to the following articles, with detailed explanations below: - "The effects of MCA-MAO on cAMP pathway in rats with cerebral hemorrhage" by Y. Jiang, X.-F. Wang, Y.-L. Niu, J.-H. Xia-Eur Rev Med Pharmacol Sci 2016; 20 (9): 1834-1838-PMID: 27212177. Readers have pointed out on PubPeer that Figures 1B and D appear to contain some overlaps. Moreover, there is no ethical approval statement for this study. The editorial team has contacted the authors but received no reply. The journal investigation revealed a figure duplication. Therefore, the Editor in Chief mistrusts the results and decided to retract the manuscript. Although the authors were notified of the retraction decision, they remained unresponsive. - "Research on the role of GLP-2 in the central nervous system EPK signal transduction pathway of mice with vascular dementia" by C.-L. Chi, S.-A. Zhang, Z. Liu, M.-X. Chang, H. Wang, Y. Huang-Eur Rev Med Pharmacol Sci 2017; 21 (1): 131-137-PMID: 28121365. Readers have pointed out on PubPeer that Figure 3 appears to contain some overlaps. Moreover, there is no ethical approval statement for this study. The editorial team has contacted the authors but received no reply. The journal investigation revealed a figure duplication. Therefore, the Editor in Chief mistrusts the results and decided to retract the manuscript. Although the authors were notified of the retraction decision, they remained unresponsive. - "Studies on the relationship between P13K/AKT signal pathway-mediated MMP-9 gene and lung cancer" by H. Zheng, J.-F. Liu-Eur Rev Med Pharmacol Sci 2017; 21 (4): 753-759-PMID: 28272723. Readers on PubPeer have expressed concerns about Western blots, as shown in Figure 2. Moreover, there is no ethical approval statement for this study. The editorial team has contacted the authors but received no reply. The journal investigation did not detect figure manipulation; however, since the lack of ethics statement and the lack of the original data, the Editor in Chief decided to retract the manuscript. Although the authors were notified of the retraction decision, they remained unresponsive. - "LncRNA LINC01116 competes with miR-145 for the regulation of ESR1 expression in breast cancer" by H.-B. Hu, Q. Chen, S.-Q. Ding-Eur Rev Med Pharmacol Sci 2018; 22 (7): 1987-1993-DOI: 10.26355/eurrev_201804_14726-PMID: 29687853. Readers on PubPeer have expressed concerns regarding inconsistencies between data presented in Tables and figures, deficiencies in the description of sample collection, and a lack of ethics approval. The editorial team has contacted the authors to request the raw data of the manuscript and a reply to those concerns but has not received any response. Throughout the journal investigation, numerous flaws and inconsistencies were discovered in the presented results. Therefore, the editors deem the conclusions of this article to be invalid and decided to retract the manuscript. The corresponding author did not respond to journal correspondence about the investigation and retraction of this article. These articles have been retracted. The Publisher apologizes for any inconvenience this may cause.

LINC00460 promotes neuroblastoma tumorigenesis and cisplatin resistance by targeting miR-149-5p/DLL1 axis and activating Notch pathway invitro and in vivo.

Long noncoding RNAs (lncRNAs) have been demonstrated to participate in neuroblastoma cisplatin resistance and tumorigenesis. LncRNA LINC00460 was previously reported to play a critical regulatory role in many cancer development. Nevertheless, its role in modulating neuroblastoma cisplatin resistance has not been explored till now. Cisplatin-resistant neuroblastoma cell lines were established by exposing neuroblastoma cell lines to progressively increasing concentrations of cisplatin for 6months. LINC00460, microRNA (miR)-149-5p, and delta-like ligand 1 (DLL1) mRNA expression was measured through RT-qPCR. The protein levels of DLL1, epithelial-to-mesenchymal transition (EMT) markers, and the Notch signaling-related molecules were measured via western blotting. The IC50 value for cisplatin, cell growth, metastasis and apoptosis were analyzed in cisplatin-resistant neuroblastoma cells. The binding between LINC00460 (or DLL1) and miR-149-5p was validated through dual-luciferase reporter assay. The murine xenograft model was established to perform in vivo assays. LINC00460 and DLL1 levels were elevated, while miR-149-5p level was reduced in cisplatin-resistant neuroblastoma cells. LINC00460 depletion attenuated IC50 values for cisplatin, weakened cell growth, metastasis, and EMT, and enhanced apoptosis in cisplatin-resistant neuroblastoma cells. Mechanically, LINC00460 sponged miR-338-3p to increase DLL1 level, thereby activating Notch signaling pathway. DLL1 overexpression antagonized LINC00460 silencing-induced suppression on neuroblastoma cell cisplatin resistance and malignant behaviors, while such effects were further reversed by treatment with DAPT, the inhibitor of Notch pathway. Additionally, LINC00460 knockdown further augmented cisplatin-induced impairment on tumor growth in vivo. LINC00460 contributes to neuroblastoma cisplatin resistance and tumorigenesis through miR-149-5p/DLL1/Notch pathway, providing new directions to improve the therapeutic efficacy of chemotherapy drugs applied in patients with neuroblastoma.

LINC00460 knockdown sensitizes cervical cancer to cisplatin by downregulating TGFBI.

The acquired resistance of cancer to cisplatin (DDP) limits the efficacy of chemotherapy. The prognostic value of long noncoding RNA (lncRNA) LINC00460 has been reported in cervical cancer. However, its effect on DDP sensitivity in cervical cancer remains poorly understood. In present study, LINC00460 was screened out through bioinformatics analysis. The expression levels of mRNAs and proteins were measured by reverse transcription-quantitative PCR (RT-qPCR) or western blot analysis. The sensitivity to DDP was investigated using an CCK8 assay. Cell apoptosis was determined by flow cytometry. The differentially expressed genes that were associated with the poor prognosis of cervical cancer were screened, and their correlations with LINC00460 expression were explored using Pearson's correlation analysis. Tumor xenograft model was used to assess the effect of LINC00460 knockdown on DDP sensitivity invivo. The interaction between miR-338-3p and LINC00460 or transforming growth factor β-induced protein (TGFBI) was confirmed by RNA immunoprecipitation (RIP) and luciferase reporter assays. LINC00460 expression was increased in cervical cancer tissues and cells. High expression of LINC00460 was associated with dismal prognosis in cervical cancer patients. Silencing of LINC00460 increased drug sensitivity and induced apoptosis in DDP-resistant-cervical cancer cells. LINC00460 knockdown enhanced DDP sensitivity in cervical cancer cells largely by downregulating TGFBI expression. LINC00460 knockdown enhanced the sensitivity of cervical cancer to DDP invivo, and this effect was partly mediated by the downregulation of TGFBI. LINC00460 positively regulated TGFBI expression, possibly by acting as a sponge of miR-338-3p. LINC00460 knockdown contributed to DDP sensitivity of cervical cancer by downregulating TGFBI, providing a novel mechanism underlying the acquisition of DDP sensitivity.

Upregulation of long non‑coding RNA LINC00460 in EGFR‑mutant lung cancer indicates a poor prognosis in patients treated with osimertinib.

The long non-coding RNA (lncRNA) LINC00460 is involved in tumor growth, metastasis and drug resistance. The present study investigated the clinical significance of LINC00460 expression in patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer treated with osimertinib. Osimertinib-resistant cells we derived from EGFR-mutant non-small-cell lung cancer (NSCLC) cell lines, after which, small interfering RNA (siRNA)-mediated silencing and in vitro-transcribed (IVT), synthetic LINC00460 RNA transfection were used to investigate the effects of LINC00460 expression on acquired resistance to osimertinib. Reverse transcription-quantitative polymerase chain reaction was performed to evaluate LINC00460 expression in 54 samples (RNA extracted from the tumor tissues of 30 cases and cell-free RNA from 24 cases) obtained from patients with EGFR mutation-positive lung cancer who had received osimertinib as the initial treatment. The acquisition of osimertinib resistance increased the expression of LINC00460 in the EGFR-mutant NSCLC cell lines. By contrast, knockdown of LINC00460 in osimertinib-resistant cell lines increased their sensitivity to osimertinib, whereas treatment of NSCLC cells with IVT LINC00460 RNA decreased their sensitivity to osimertinib. The present study examined LINC00460 expression at the primary tumor site and demonstrated that compared with in the low-expression group (n=24), the high-expression group (n=6) had a significantly lower best overall response rate to osimertinib (16.6% vs. 60.0%; P=0.044), significantly shorter median progression-free survival (PFS; 224 days vs. 669 days; P=0.001) and significantly shorter median overall survival (724 days vs. not reached; P=0.011). Moreover, following osimertinib therapy, PFS was significantly shorter for patients with high LINC00460 expression in plasma cell-free RNA (n=12) than for those with low LINC00460 expression (n=12) (median PFS: 655 days vs. 210 days; P=0.020). In conclusion, the upregulation of LINC00460, the expression of which is implicated in osimertinib resistance, in the primary site and plasma of patients with EGFR mutation-positive lung cancer may be associated with a poor prognosis in those treated with osimertinib.

LncRNA LINC01116 Contributes to Cisplatin Resistance in Lung Adenocarcinoma [Retraction

[This retracts the article DOI: 10.2147/OTT.S244879.].

Small peptide LINC00511-133aa encoded by LINC00511 regulates breast cancer cell invasion and stemness through the Wnt/β-catenin pathway

LINC00511 is an long non-coding RNA (lncRNA) of ncRNAs,This study aimed to investigate whether the lncRNA LINC00511 could encode a small peptide, LINC00511-133aa, and whether this peptide could promote breast cancer cell metastasis and stemness by activating the wnt/β-catenin pathway. The LINC00511-133aa coding sequence vector and control vector were transfected into MCF-7 and MDA-MB-231 breast cancer cells, with subsequent assessment of peptide expression using PCR, western blotting, and immunofluorescence assays. Cell proliferation, invasion, and apoptosis were evaluated using CCK8, apoptotic, wound healing, and transwell invasion assays, while the characteristic changes of tumor stem cells were detected through sphere-forming assay and western blot analyses of the stemness markers Oct4, Nanog, and SOX2. Results showed that LINC00511-133aa was indeed encoded by LINC00511 and promoted the invasiveness and stemness of breast cancer cells while limiting apoptosis by modulating the expression levels of wnt/β-catenin pathway-related proteins Bax, c-myc, and CyclinD1, as well as facilitating β-catenin protein entry into the nucleus. This study provides evidence for the potential involvement of lncRNA LINC00511 and its peptide product in breast cancer progression via the regulation of the wnt/β-catenin pathway.

Exosomal LINC00460/miR-503-5p/ANLN positive feedback loop aggravates pancreatic cancer progression through regulating T cell-mediated cytotoxicity and PD-1 checkpoint.

Long non-coding RNA (lncRNA) LINC00460 is an onco-lncRNA in a variety of cancers, including pancreatic cancer (PC). This study is aimed to investigate the regulatory mechanisms of LINC00460 in PC. The tumor and adjacent normal tissues were collected from 73 PC patients. The expression of LINC00460, miR-503-5p, and ANLN was detected using qRT-PCR. We then analyzed the proliferation, migration, invasion, and apoptosis/cell cycle of PC cells by performing the MTT/EdU, transwell, and flow cytometry assays, respectively. The xenograft tumor model were utilized to confirm the effect of LINC00460 knockdown on PC through anti-PD-1 therapy in vivo, and the sensitivity of PANC-1 cells to the cytotoxicity of CD8+ T cells in vitro. Western blotting was used to determine the protein levels. A co-culture model was utilized to explore the effects of exosomes on macrophages. LINC00460 was up-regulated in PC tissues and cells. LINC00460 knockdown suppressed cell proliferation, migration, and invasion, facilitated cell apoptosis and G0/G1 phase arrest, and inhibited the tumor growth through anti-PD-1 therapy. Both miR-503-5p down-regulation and ANLN up-regulation reversed the effects of LINC00460 knockdown on inhibiting the proliferation, migration and invasion, and on promoting the apoptosis, G0/G1 phase arrest, and the sensitivity of PC cells to the cytotoxicity of CD8+ T cells. Exosomes were uptaken by the ambient PC cells. PANC-1 cells-derived exosomal LINC00460-induced M2 macrophage polarization accelerates the cell migration and invasion. LINC00460 silencing attenuates the development of PC by regulating the miR-503-5p/ANLN axis and exosomal LINC00460-induced M2 macrophage polarization accelerates the migration and invasion of PANC-1 cells, thus LINC00460 may act as a possible therapeutic target for treating PC.

LINC00511 promotes cervical cancer progression by regulating the miR-497-5p/MAPK1 axis

BackgroundLong non-coding RNA (lncRNA) exhibits a crucial role in multiple human malignancies. The expression of lncRNA LINC00511, reportedly, is aberrantly up-regulated in several types of tumors. Our research was aimed at deciphering the role and mechanism of LINC00511 in the progression of cervical cancer (CC).MethodQuantitative real-time polymerase chain reaction (qRT-PCR) was performed to quantify the expression levels of LINC00511, miR-497-5p and MAPK1 mRNA in CC tissues and cell lines. Cell counting kit-8 (CCK-8), 5-bromo-2’-deoxyuridine (BrdU) and Transwell assays were conducted for detecting the proliferation, migration and invasion of CC cells. Dual-luciferase reporter gene experiments were performed to verify the targeting relationships amongst LINC00511, miR-497-5p and MAPK1. Besides, MAPK1 expression in CC cells was detected via Western blot after LINC00511 and miR-497-5p were selectively regulated.ResultsUp-regulation of LINC00511 expression in CC tissues and cell lines was observed, which was in association with tumor size, clinical stage and lymph node metastasis of the patients. LINC00511 overexpression facilitated the proliferation, migration and invasion of CC cells, while opposite effects were observed after knockdown of LINC00511. Mechanistically, LINC00511 was capable of targeting miR-497-5p and up-regulating MAPK1 expression.ConclusionLINC00511/miR-497-5p/MAPK1 axis regulates CC progression.

Multiomics Immune-Related lncRNA Analysis of Oral Squamous Cell Carcinoma and Its Correlation with Prognosis.

Objective To investigate the multiomics immune-related lncRNA analysis of oral squamous cell carcinoma and its correlation with prognosis. Methods Through the bioinformatics database, a total of 346 oral squamous cell carcinoma (OSCC) related samples were retrieved. Bioinformatics analysis screened out the difference lncRNAs in the sample tissue and normal tissue, combined with literature research to clarify the target. The biological functions of differentially expressed lncRNAs were predicted. The differential expression network of differentially expressed lncRNAs and mRNAs was established. The correlation analysis software was used to analyze the correlation between oral squamous cell carcinoma multiomics immune-related lncRNA and prognosis. Results 3054 lncRNAs in OSCC tissues are highly correlated with immune genes. 76 immune-related lncRNAs were different in tumor and adjacent tissues. Cancer Hallmark, Phenotype, and Subcellular Location analysis were completed. The results showed that lncRNAs can participate in tumor cell invasion, metastasis, proliferation, and apoptosis. Select the 15 most important lncRNAs above, draw Kaplan-Meier curve to complete the survival curve analysis, and complete the analysis and arrangement of the relevant data. LINC00460, CASC9, and HCG22 were screened for subsequent analysis. Complete the GO and KEGG enrichment analysis. LINC00460, CASC9, and macrophages M0 are positively correlated; CASC9 is negatively correlated with macrophages M1; LINC00460 is positively correlated with macrophages M1; HCG22 is associated with mast cells resting positive correlation; LINC00460 was negatively correlated with mast cell resting. CASC9 and HCG22 were significantly correlated with the age and stage of OSCC patients; 2 key lncRNA and 79 miRNAs were extracted from the database, to complete 86 pairs of interactions; the target mRNAs were predicted based on the above miRNAs. A total of 631 pairs of interactions were predicted (including 21 miRNAs and 562 mRNAs), and the regulatory mechanism of key gene ceRNA network was constructed. Conclusion The differential expression of multiple lncRNAs and mRNAs was screened, and the downregulated lncRNAs were more than the upregulated lncRNAs. The lncRNA LINC00460, CASC9, and HCG22 had a strong correlation with prognosis.

LncRNA LINC00511 promotes COL1A1-mediated proliferation and metastasis by sponging miR-126-5p/miR-218-5p in lung adenocarcinoma

BackgroundLung adenocarcinoma (LUAD) is currently the leading cause of cancer-related death worldwide. Long noncoding RNAs (lncRNAs) play key roles in tumor occurrence and development as crucial cancer regulators. The present study aimed to explore the molecular mechanism and regulatory network of Linc00511 in LUAD and to identify new potential therapeutic targets for LUAD.MethodsReal-time quantitative polymerase chain reaction (RT–qPCR) was performed to determine the relative Linc00511 levels in LUAD tissues and cells. The proliferation, apoptosis, migration, and invasion abilities of LUAD cells were assessed by a Cell Counting Kit-8 (CCK-8) assay, a colony formation assay, flow cytometry, and a Transwell assay. Changes in hsa_miR-126-5p, hsa_miR-218-5p, and COL1A1 expression were analyzed using western blotting and RT–qPCR. Targeted binding between miR-126-5p/miR-218-5p and Linc00511 or COL1A1 was verified with a luciferase reporter system and confirmed by an RNA pulldown assay. The participation of the PI3K/AKT signaling pathway was confirmed via western blotting. Xenograft animal experiments were performed to detect the impact of Linc00511 on LUAD tumor growth in vivo.ResultsIn the present work, we observed that Linc00511 was upregulated in LUAD tissues and cells. Loss/gain-of-function experiments indicated that knockdown of Linc00511 significantly inhibited LUAD cell proliferation, migration and invasion and promoted LUAD cell apoptosis, whereas overexpression of Linc00511 showed the opposite effects. In addition, we determined that Linc00511 promoted COL1A1-mediated cell proliferation and cell motility by sponging miR-126-5p and miR-218-5p. Moreover, Linc00511 activated the PI3K/AKT signaling pathway through upregulation of COL1A1. Finally, silencing of Linc00511 inhibited LUAD tumor growth in vivo.ConclusionsLinc00511 acts as a competing endogenous RNA to regulate COL1A1 by targeting miR-126-5p and miR-218-5p, thereby promoting the proliferation and invasion of LUAD cells.

LncRNA LINC01116 Regulates the Proliferation, Migration, and Invasion of Cervical Cancer Cells by Targeting miR-744-5p

Objective. To investigate the effects and potential molecular mechanisms of LncRNA LINC01116 on proliferation, migration, and invasion of cervical cancer cells. Method(s). The content of miR-744-5p and LINC01116 in cervical cancer cells HeLa, SiHa, and C33a was detected by RT-PCR, the proliferative activity and clone number of SiHa cells were determined by MTT and clone formation assay, the number of invaded and migrated cells was determined by Transwell assay, the expressions of Cyclin D1 and MMP-2 in cells were detected by Western blot, and the activity of luciferase detected by dual-luciferase reporting system verified the regulatory relationship between LINC01116 and miR-744-5p. Result(s). Compared with human normal cervical epithelial cells Ect1/E6E7, the content of LINC01116 in cervical cancer cells HeLa, SiHa, and C33a was increased significantly [( 1.04 ± 0.12 ) vs. ( 3.34 ± 0.38 )/( 4.48 ± 0.45 )/( 3.59 ± 0.45 )] ( P < 0.05 ), the content of miR-744-5p was decreased significantly [( 0.98 ± 0.09 ) vs. ( 0.39 ± 0.04 )/( 0.34 ± 0.05 )/( 0.41 ± 0.05 )] ( P < 0.05 ). Silencing LINC01116 could inhibit the protein expression of Cyclin D1 [( 0.68 ± 0.06 ) vs. ( 0.31 ± 0.04 )] and MMP-2 [( 0.74 ± 0.08 ) vs. ( 0.34 ± 0.05 )] in SiHa cells, and inhibition of cell proliferation [( 100.98 ± 7.89 )% vs. ( 67.26 ± 6.14 )%], clone formation ability [( 180.31 ± 11.34 ) vs. ( 53.56 ± 6.18 )], migration [( 234.67 ± 15.31 ) vs. ( 98.46 ± 7.46 )], and invasion [( 134.83 ± 9.12 ) vs. ( 62.44 ± 5.34 )]. LINC01116 targeted and negatively regulates the expression of miR-744-5p. Overexpression of miR-744-5p could inhibit the proliferation of cervical cancer SiHa cells [( 101.64 ± 4.89 )% vs. ( 62.34 ± 5.73 )%], clone formation ability [( 179.24 ± 12.34 ) vs. ( 47.67 ± 5.18 )], migration [( 241.06 ± 16.64 ) vs. ( 84.52 ± 7.57 )], and invasion [( 127.92 ± 8.16 ) vs. ( 65.24 ± 7.36 )]. Inhibition of miR-744-5p reversed the effects of silencing LINC01116 on SiHa cell proliferation [( 102.46 ± 7.64 )% vs. ( 146.72 ± 12.23 )%], clone formation ability [( 47.64 ± 6.20 ) vs. ( 104.26 ± 8.64 )], migration [( 81.52 ± 7.42 ) vs. ( 153.64 ± 12.57 )], and invasion [(69.12 ± 5.56) vs (94.31 ± 7.44)]. Conclusion(s). LncRNA LINC01116 inhibits proliferation, migration, and invasion of SiHa cells by targeting miR-744-5p, and LINC01116 is a potential molecular target for cervical cancer.

LncRNA LINC00460 facilitates the proliferation and metastasis of renal cell carcinoma via PI3K/AKT signaling pathway.

Renal cell carcinoma (RCC) is one of the most prevalent cancers diseases in the worldwide. Long noncoding RNAs (LncRNAs) have been indicated as a mediator acted in tumorigenesis of RCC. LINC00460 has been reported to participate in many kinds of malignancies and promotes cancer progressions. However, the mechanism of LINC00460 on RCC is yet to be investigated. This study aimed to explore the potential function and regulation mechanism of LINC00460 in RCC. We analysed the LINC00460 expression and the prognosis in RCC patients using Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) databases. LINC00460 level in normal renal cell line and RCC cell lines were examined by qRT-PCR. We study the effects of LINC00460 on proliferation, migration, invasion, apoptosis in RCC cells lines using a series of in vivo and in vitro experiments. RNA sequencing (RNA-seq) analysis was applied to searching potential LINC00460 related signal pathway in RCC. We identified the significant up-regulated expression of LINC00460 both in RCC tissues and cell. RCC patients with elevated LINC00460 expression have shorter survival. Up-expression of LINC00460 promoted cell proliferation, invasion and migration, meanwhile down-regulation of LINC00460 exerted inhibitory effect on these activities. We crucially identified that LNC00460 promotes development of RCC by influencing the PI3K/AKT pathway. Knockdown of LNC00460 decreased the phosphorylation of AKT and mTOR. The key finding of our study showed that LINC00460 functions as an oncogene in RCC pathogenesis by mediating the PI3K/AKT.

Long non-coding RNA LINC00511 promotes proliferation, invasion, and migration of non-small cell lung cancer cells by targeting miR-625-5p/GSPT1.

BackgroundLung cancer is a malignant tumor with a high rate of mortality and metastasis. Recently, extensive research has shown that long non-coding RNAs (lncRNAs) play a crucial role in the development and progression of non-small cell lung cancer (NSCLC). In this paper, we aimed to explore the impact of long intergenic non-coding RNA 00511 (LINC00511) on the development and metastasis of NSCLC.MethodsA dataset containing 501 lung squamous cell carcinoma (LUSC) samples and 49 normal samples was downloaded from The Cancer Genome Atlas (TCGA). The differential gene expression and prognostic potential of LINC00511 in LUSC were analyzed by “limma” in R software. Samples of tumor tissues and normal tissues from 67 patients with NSCLC were obtained, along with clinical features. NSCLC cell proliferation, cell cycle, migration, and invasion were detected by LINC00511 knockdown with Cell Counting Kit-8 (CCK-8), flow cytometry, wound-healing assay, and Transwell experiment. The regulatory relationship between LINC00511 and microRNA (miR)-625-5p, or between miR-625-5p and G1 to S phase transition 1 (GSPT1), was detected by luciferase reporter gene assay. LINC00511, miR-625-5p, and GSPT1 expression in tumor and normal tissues and cells was determined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. A xenograft experiment in nude mice was performed. Ki67 and GSPT1 expression in the tumor tissues of the nude mice was assessed by immunohistochemistry.ResultsLINC00511 expression was clearly higher in the tumor tissues of the NSCLC patients than in normal tissues (P<0.001). High LINC00511 expression was related to larger tumor size, positive lymph node metastasis, advanced TNM stage, and a lower 5-year survival rate. Compared with those of the shNC group, the NSCLC cells of the shLINC00511 group had a prominently lower optical density (OD) 450 value at 72 h, a lower percentage of cells in S phase, a higher relative wound width, and a lower invasive cell number (P<0.01 or P<0.001). LINC00511 promoted GSPT1 expression via suppressing miR-625-5p. Compared with those of the shNC group, the nude mice of the shLINC00511 group had a much lower subcutaneous tumor volume and weight (P<0.05 or P<0.001).ConclusionslncRNA LINC00511 promotes proliferation, invasion, and migration of NSCLC cells by targeting miR-625-5p/GSPT. LINC00511 may be a potential diagnostic marker and therapeutic target for NSCLC.

LncRNA LINC00460: Function and mechanism in human cancer.

Long non‐coding RNAs (LncRNAs), which are more than 200 nucleotides in length and with limited protein‐coding potential, play vital roles in the pathogenesis, tumorigenesis, and angiogenesis of cancers. Aberrant expression of lncRNAs has been detected in various carcinomas and may be correlated with oncogenesis by affecting related genes expression. Recently, an increasing number of studies have reported on long intergenic non‐protein coding RNA 460 (LINC00460) in human tumor fields. LINC00460 is upregulated in diverse cancer tissues and cells. The upregulated expression level of LINC00460 is correlated with larger tumor size, tumor node metastasis (TNM) stage, lymph node metastasis, and shorter overall survival. The regulatory mechanism of LINC00460 was complex and diverse. LINC00460 could act as a competitive endogenous RNA (ceRNA), directly bind with proteins or regulate multiple pathways, which affected tumor progression. Moreover, LINC00460 was also identified to increase drug resistance, and therefore, weaken the effectiveness of tumor treatment. It has become increasingly important to investigate the roles of LINC00460 in various cancers by different mechanisms. Therefore, a more comprehensive understanding of LINC00460 is crucial to expound on the cellular function and molecular mechanism of human cancers. In this review, we refer to studies concerning LINC00460 and provide the basis for the evaluation of LINC00460 as a predicted biomarker or potential therapeutic target in malignancies, and also provide ideas for the future research of lncRNAs similar to LINC00460.

Aberration of lncRNA LINC00460 is a Promising Prognosis Factor and Associated with Progression of Clear Cell Renal Cell Carcinoma.

PurposeLong noncoding RNAs have been studied more and more as potential prognostic markers. However, the prognostic of LINC00460 in clear cell renal cell carcinoma (ccRCC) has not been explored. In this study, the potential role of LINC00460 was investigated in ccRCC.Patients and MethodsOne hundred thirteen pairs of ccRCC tissues and para-normal tissues were collected. The expressions of LINC00460 in these tissues and ccRCC cells were evaluated via qRT-PCR. The prognostic value of LINC00460 was accessed with the use of Kaplan–Meier analysis and Cox proportional hazards model analysis. The influence of LINC00460 on ccRCC cell proliferation, migration, and invasion was determined via cell counting kit-8 (CCK-8) and Transwell assays.ResultsThe results revealed that LINC00460 was significantly enhanced in ccRCC tissues, as well as in ccRCC cell lines. The overexpression of LINC00460 was significantly associated with lymph node metastasis and TNM stage, and lead to poor overall survival. Knockdown of LINC00460 reduces the cell ability of proliferation, migration, and invasion. LINC00460 could sponge to miR-149-5p.ConclusionLINC00460 may be developed as a prognostic biomarker and molecular therapy target for ccRCC.

Long non-coding RNA LINC01116 acts as an oncogene in prostate cancer cells through regulation of miR-744-5p/UBE2L3 axis

BackgroundLong non-coding RNA (lncRNA) has been confirmed to exert a critical effect on the progression of tumors, including prostate cancer. Previous literature has demonstrated LINC01116 involves in activities of multiple cancers. However, the underlying role of LINC01116 in prostate cancer remains unclear.MethodsqRT-PCR measured the expression of LINC01116 in prostate cancer cells. EdU experiment was used to detect cell proliferation. Transwell assays detected cell migration and invasion. Immunofluorescence staining and western blot assays were utilized to measure EMT progress. The binding relationship between RNAs was confirmed by a series of mechanism assays. In addition, rescue experiments were conducted to verify the relationship among RNAs.ResultsLINC01116 was found to be highly expressed in prostate cancer cells. Functional assays indicated that inhibition of LINC01116 could suppress cell proliferation, migration, invasion and EMT progress. Also, miR-744-5p was proven to bind with LINC01116. Moreover, UBE2L3 was verified as the target gene of miR-744-5p. In rescue assays, we discovered that inhibited miR-744-5p or overexpressed UBE2L3 could offset the suppressive influence of silencing LINC01116 on prostate cancer cells.ConclusionOur study suggested that lncRNA LINC01116 acted as an oncogene in prostate cancer and accelerated prostate cancer cell growth through regulating miR-744-5p/UBE2L3 axis.

LncRNA LINC01116 sponges miR-93-5p to promote cell invasion and migration in small cell lung cancer

BackgroundLINC01116 is a recently identified oncogenic lncRNA in glioma. Differential expression analysis using the public gene expression analysis tool GEPIA revealed the upregulation of LINC01116 in lung cancer. We studied the functions of LINC01116 in small cell lung cancer (SCLC).MethodsThe expression of LINC01116 in several types of cancer tissue and the paired non-tumor tissues was evaluated by GEPIA. The effects of the overexpression of LINC01116 and miR-93-5p on the expression of STAT3 were evaluated. The effects of the overexpression of LINC01116, miR-93-5p and STAT3 on SHP-77 cell behaviors were evaluated by Transwell assays.ResultsLINC01116 was highly expressed in SCLC and predicted poor survival. In SCLC tissues, the expression of LINC01116 was positively correlated with STAT3. Bioinformatics analysis revealed that miR-93-5p may target LINC01116. Overexpression of LINC01116 increased STAT3 but did not affect the expression of miR-93-5p. Transwell assay showed that LINC01116 and STAT3 increased cell invasion and migration rates. MiR-93-5p played an suppressed cell behaviors and suppressed the role of LINC01116.ConclusionTherefore, LINC01116 might upregulate STA3 by sponging miR-93-5p, thereby promoting cell invasion and migration in SCLC.