LINC00152 Expression Research Articles

Highly Expressed LINC00958 Modulates the Growth and Epithelial-Mesenchymal Transition of Bladder Cancer Cells Through SAPK/JNK Signaling Pathway.

Objective: To determine the expression of LINC00958 (BLACAT2) in bladder cancer (BC), the most common malignancy in the urinary system, and to determine its exact mechanism of action, so as to provide novel references for future clinical diagnosis and treatment of BC and lay a foundation for the follow-up research on LINC00958. Materials and Methods: Human bladder transitional cell carcinoma cells (T24 and J82) and human normal urothelial cells (SV-HUC-1) were purchased to detect the expression of LINC00958 and SAPK/JNK signaling pathway-related proteins. sh-LINC00958 targeting to silence LINC00958 expression and corresponding negative blank (sh-Control) were transfected into T24 and J82. Additionally, BC cells cultured with SP600125 (SP600125 group), a specific inhibitor of SAPK/JNK signaling pathway, and those cultured with the same amount of normal saline (Blank group) were also constructed. Cell growth capacity, cell invasiveness, and expression of epithelial-mesenchymal transition (EMT)-associated proteins were determined using CCK-8 & clone formation assays, Transwell assay, and Western blot, respectively. Results: The online databases Gene Expression Profiling Interactive Analysis, European Bioinformatics Institute, and StarBase revealed elevated LINC00958 expression in BC, and a potential association between LINC00958 and patient prognosis and survival. PCR results showed that LINC00958 was increased in T24 and J82 compared with the sh-Control group (p < 0.05). The results of biological behavior test revealed that the proliferation and invasiveness capacity of the sh-LINC00958 group decreased, while that of the SP600125 group increased compared with the Blank group (both p < 0.05). In the rescue experiment, the influence of sh-LINC00958 on BC cells was completely reversed by SP600125 (p > 0.05); In addition, the expression of E-cadherin, an EMT marker protein, was lower compared with the SH-LINC0958 group, while the Vimentin expression was higher (p < 0.05). Similarly, the wound-healing assay determined reduced cell healing rate in the sh-LINC00958 group (p < 0.05), and there was no difference between the sh-LINC00958+SP600125 group and the sh-Control group (p > 0.05). Conclusion: LINC00958 shows elevated expression in BC and promotes the growth and EMT of BC cell via inhibiting the SAPK/JNK signaling pathway, which has important potential as a new clinical diagnostic marker and therapeutic target for BC.

LINC00963 May Be Associated with a Poor Prognosis in Patients with Cervical Cancer.

BackgroundRecently, the upregulation of LINC00963 expression has been reported in various cancer subtypes. LINC00963 expression can promote cancer cell invasion and metastasis. However, the clinical significance of LINC00963 in cervical and endocervical cancer (CESC) has remained relatively unexamined.Material/MethodsWe assessed the mRNA expression of LINC00963 in patients with CESC based on data acquired from The Cancer Genome Atlas (TCGA) to determine pathways involved in CESC pathogenesis with respect to LINC00963. We included 3 normal and 304 tumor samples in this study.ResultsThe scatter plot and paired plot showed differences in LINC00963 expression between normal and tumor samples (P<0.01). Overall survival (OS) analysis revealed that CESC patients with high expression of LINC00963 demonstrated worse prognosis than CESC patients with low expression of LINC00963 (P<0.01). Multivariate analysis with the Cox proportional hazards model indicated that the expression of LINC00963 (HR 0.297; 95% CI 0.115–0.776; P=0.012) and primary therapy outcome (HR 0.162; 95% CI 0.059–0.446; P=0.001) were independent prognostic factors for patients with CESC. GSEA results showed that reactome biological oxidations, inflammasomes, apoptosis, toll-like receptor signaling pathway, JAK/STAT signaling pathway, and NF-κB activation were differentially enriched in CESC samples with the high LINC00963 expression phenotype.ConclusionsOur results confirmed the association of significantly high levels of LINC00963 expression in CESC with several observed clinical features. LINC00963 may be a potentially useful prognostic molecular biomarker associated with poor survival in patients with CESC.

Deoxyelephantopin Suppresses Pancreatic Cancer Progression In Vitro and In Vivo by Targeting linc00511/miR-370-5p/p21 Promoter Axis.

Objectives Deoxyelephantopin (DET) is a kind of natural active ingredient extracted from the Chinese herbal medicine Elephantopus scaber L. Many studies have revealed the potential antitumor effect on multiple malignancies. However, the detailed mechanism of its antitumor effect in pancreatic cancer remains unclear. Recently, studies have confirmed that noncoding RNA (ncRNA) plays an important regulatory role in malignancies. This research was performed to explore the relationship between ncRNA and DET-induced tumor inhibition in pancreatic cancer. Methods Microarray profiling was applied to identify the candidate ncRNAs associated with DET-induced tumor inhibition. Quantitative real-time PCR was used to evaluate the expression of linc00511 in pancreatic cancer cells and tissues. The influence of DET on the cell proliferation, migration, and invasion was assessed by CCK-8, colony formation, wound healing, and Transwell assays. The relationship between lncRNAs, miRNAs, and p21 promoter region was analyzed by bioinformatics and verified by luciferase reporter gene and western blotting. The effect of linc00511 on nuclear translocation of miR-370-5p was explored by cytoplasmic and nuclear RNA purification. Moreover, the effect of DET on tumor growth and metastasis, and the prophylactic effect were investigated by establishing subcutaneous and lung metastatic tumor models. Results Microarray assay indicated linc00511 was a potential target gene. The antitumor effect of DET in pancreatic cancer depended on downregulating linc00511 expression, and linc00511 might be an oncogene in pancreatic cancer. Silencing linc00511 enhanced the antitumor function of DET; conversely, linc00511 overexpression antagonized the DET cytotoxic effect. Additionally, miR-370-5p could bind to p21 promoter to exert the RNA activation and then promote p21 expression. P21 was a downstream gene of linc00511 and associated with pancreatic cancer progression. Linc00511 regulated p21 expression by blocking miR-370-5p nuclear translocation. Conclusions To sum up, the present finding confirmed that DET suppressed the malignant biological behavior of pancreatic cancer via linc00511/miR-370-5p/p21 promoter axis.

LINC01116 Promotes Migration and Invasion of Oral Squamous Cell Carcinoma by Acting as a Competed Endogenous RNA in Regulation of MMP1 Expression.

Oral squamous cell carcinoma (OSCC) has increasingly become a worldwide health concern, and its survival rate has not been much improved partially due to a deficiency of precise molecular markers. Dysregulation of LINC01116, a long noncoding RNA sequence, has been observed in several types of cancer. However, the role played by LINC01116 in OSCC has not yet been fully elaborated. This study explored how LINC01116 was involved in the regulation of OSCC progression by analyzing expressions of LINC01116 in OSCC patients. The findings demonstrated upregulation of LINC01116 in OSCC tissues as opposed to regular oral mucosa, and overexpression of LINC01116 was correlated with advanced tumor status. LINC01116 knockdown using shRNA markedly reduced the OSCC cell invasion and migration in vitro. Moreover, the expression of LINC01116 was negatively correlated with that of microRNA-9-5p (miR-9). Luciferase reporter and loss-of-function assays demonstrated that LINC01116 functioned as a competing endogenous RNA (ceRNA) that could effectively sponge miR-9, thus regulating the derepression of matrix metalloproteinase 1 (MMP1). Furthermore, we confirmed that LINC01116 knockdown did not affect the expression of MMP1 messenger RNA (mRNA). Collectively, it is demonstrated in this study that overexpression of LINC01116 can promote the OSCC progression. The LINC01116–miR-9-MMP1 axis provides a novel insight into the OSCC pathogenesis and offers potential therapeutic targets against OSCC.

Risk SNP-mediated LINC01614 upregulation drives head and neck squamous cell carcinoma progression via PI3K/AKT signaling pathway.

As potential biomarkers and therapeutic targets, long noncoding RNAs (lncRNAs) are involved in the tumorigenesis of various tumors. Genetic variation in long noncoding regions can lead to lncRNAdysfunction and even cancer. Nevertheless, studies on the association between lncRNA-associated single-nucleotide polymorphisms (SNPs) and the risk of head and neck squamous cell carcinoma (HNSCC) remain inadequate. Here, we aimed to explore the association between SNPs in LINC01614 and HNSCC risk, and the potential role of LINC01614 in tumorigenesis. In this study, we found that rs16854802 A > G (odds ratio [OR] = 1.42, 95% confidence interval [CI]: 1.22-1.77, p < 0.001) and rs3113503 G > C (OR = 1.38, 95%CI: 1.15-1.64, p < 0.001) in LINC01614 increased the risk of HNSCC in the Chinese population. Functional bioinformatic analysis and luciferase reporter assay revealed that rs3113503 G > C variant disrupted the binding of miRNA-616-3p to LINC01614, which resulted in the increased expression of LINC01614. Further analysis of the TCGA database demonstrated that the upregulated LINC01614 in HNSCC cancer tissues was associated with poor prognostic in HNSCC patients. In vitro experiments showed that knockdown of LINC01614 inhibited the proliferation, invasion, and migration ability of HNSCC cells. Mechanistically, allele C of rs3113503 in LINC01614 was more effective than allele G in activating the PI3K/AKT signaling pathway. Moreover, the reduced expression of LINC01614 also inhibited the activation of the PI3K/AKT signaling pathway. In summary, our findings revealed that the risk SNP rs3113503 G > C in LINC01614 altered the binding to miR-616-3p, which led to increased LINC01614 expression and promoted HNSCC progression by activating the PI3K/AKT signaling pathway.

New Sights Into Long Non-Coding RNA LINC01133 in Cancer.

LINC01133 is a long intergenic non-coding RNA that regulates malignancy in several cancers, including those of the digestive, female reproductive, respiratory, and urinary system. LINC01133 is an extensively studied lncRNA that is highly conserved, and its relatively stable expression is essential for its robust biological function. Its expression is highly tissue-specific with a distinct subcellular localization. It functions as an oncogene or a tumor suppressor gene in different cancers via multiple mechanisms, such as those that involve competing with endogenous RNA and binding to RNA-binding proteins or DNA. Moreover, the secretion and transportation of LINC01133 by extracellular vesicles in the tumor micro-environment is regulated by other cells in the tumor micro-environment. To date, two mechanisms, an increase in copy number and regulation of transcription elements, have been found to regulate LINC01133 expression. Clinically, LINC01133 is an ideal marker for cancer prognosis and a potential therapeutic target in cancer treatment regimes. In this review, we aimed to summarize the aforementioned information as well as posit future directions for LINC01133 research.

Multicenter prospective clinical trial of molecular genetic markers for non-invasive differential diagnosis of benign and malignant melanocytic skin lesions.

e21581 Background: Improving the accuracy of non-invasive diagnosis of skin tumors is becoming an urgent problem, given the clear increase in the incidence of melanoma in many countries. Dermoscopy and examination by an experienced dermatologist can reduce the NNE to 5–10 per melanoma (M) detected, however, achieving even this, clearly suboptimal, rate requires a long specialist training. Methods: We report results of prospective nonrandomized trial evaluating sensitivity and specificity of RNA profiling of cytological samples from adhesive transparent patches (ATP) applied to skin lesions. Routine pathology reports were obtained for all surgery samples. RNA extracted from ATP specimens (N = 126) was tested for mRNA expression of PRAME and LINC00518 genes. GAPDH was used as a reference gene. Sample was considered marker-positive if either PRAME or LINC00518 expression was detected. Results: Between June 2021 and November 2021, 126 pts undegoing excisional biopsy of skin lesions were included in the study at 5 centers. On pathology, invasive M was detected in 49 (38.9%) patients (mean Breslow thickness was 2.41 mm [95%CI 1,44 to 3.37]), M in situ in 6 (4.8%), non-melanoma skin cancer in 4 (3.2%) and dysplastic nevus in 56 (44.4%). In the day of preplanned excision ATP was applied to the target lesion for 5–6 min and sent to the central lab. Amplifiable mRNA was found in all 126 ATP samples. 82 samples of 126 (65,1%) tested marker-positive. Sensitivity of RNA profiling for detection of skin cancers reached 88.14% (95% CI 77.07% – 95.09%), while specificity was only 53.85% (41.03% – 66.30%), with PPV of 63.41% (56.74% – 69.61%), NPV of 83.33% (70.65% – 91.22%) and accuracy of 70.16% (61.29% – 78.04%). Among the seven false negative results there were 3 M in situ and 4 invasive M. Conclusions: RNA profiling of skin ATP specimens is feasible and has high sensitivity but rather low specificity. Randomized studies are needed to evaluate if this technique can add anything to dermoscopy or other noninvasive diagnostic modalities. Clinical trial information: NCT04353050. [Table: see text]

LINC00662 enhances cell progression and stemness in breast cancer by MiR-144-3p/SOX2 axis

BackgroundBreast cancer (BC) is one of the most prevalent malignancies among women globally. Emerging evidence indicates that long non-coding RNAs (lncRNAs) are associated with BC carcinogenesis. In the current study, we explored the mechanism by which LINC00662 regulates BC.MethodsQuantitative real-time PCR (qRT-PCR) assessed RNA expressions while western blot for protein levels. Kaplan Meier analysis evaluated overall survival (OS). Cytoplasmic/nuclear fractionation, RNA binding protein immunoprecipitation (RIP) and luciferase reporter assays probed into the underlying molecular mechanism of LINC00662 in BC. Xenograft model was established to explore the influence of LINC00662 on BC progression in vivo. R square graphs were utilized to represent RNA relationships.ResultsLINC00662 is overtly overexpressed in BC tissues and cell lines. LINC00662 knockdown hampers cell proliferation, migration, invasion and stemness. LINC00662 expression is negatively correlated with OS of BC patients. LINC00662 up-regulates SOX2 expression by competitively binding to miR-144-3p, thereby modulating BC cell progression. Xenograft experiments verified that LINC00662 promotes BC tumor growth and cell stemness in vivo.ConclusionLINC00662 enhances cell proliferation, migration, invasion and stemness in BC by targeting miR-144-3p/SOX2 axis. The findings in the present study suggested that LINC00662 could be a potential therapeutic target for BC treatment.Graphical

LINC00665: An Emerging Biomarker for Cancer Diagnostics and Therapeutics.

Long intergenic noncoding RNA 00665 (LINC00665) is located on human chromosome 19q13.12. LINC00665 was upregulated in eighteen cancers and downregulated in two cancers. LINC00665 not only inhibits 25 miRNAs but also directly affects the stability of ten protein-coding genes. Notably, LINC00665 also encodes a micro-peptide CIP2A-BP that promotes triple-negative breast cancer progression. LINC00665 can participate in five signaling pathways to regulate cancer progression, including the Wnt/β-catenin signaling pathway, TGF-β signaling pathway, NF-κB signaling pathway, PI3K/AKT signaling pathway, and MAPK signaling pathway. Aberrant expression of LINC00665 in breast cancer, gastric cancer, and hepatocellular carcinoma can be used for disease diagnosis. In addition, aberrant expression of LINC00665 is closely associated with clinicopathological features and poor prognosis of various cancers. LINC00665 is closely associated with the effects of anticancer drugs, including gefitinib and cisplatin in non-small cell lung cancer, gemcitabine in cholangiocarcinoma, and cisplatin-paclitaxel in breast cancer. This work systematically summarizes the diagnostic and prognostic values of LINC00665 in various tumors, and comprehensively analyzes the molecular regulatory mechanism related to LINC00665, which is expected to provide clear guidance for future research.

Downregulated Reprimo by LINC00467 participates in the growth and metastasis of gastric cancer

ABSTRACT Gastric cancer (GC) as an aggressive malignancy still causes a global health problem. It has been documented that long noncoding RNAs are involved in GC development. Therefore, this research was designed to explore the role of LINC00467 in the growth and metastasis of GC. The expression of LINC00467 and Reprimo in GC tissues and cells was detected. The binding relationship among LINC00467, DNA methyltransferase 1 (DNMT1) and Reprimo was assessed following. Reprimo promoter methylation was detected by methylation sequencing. GC cell lines overexpressing or knock downing LINC00467 were constructed for pinpointing the effect of LINC00467 on cell functions as well as growth and metastasis of GC cells in vivo. LINC00467 was highly expressed, whereas Reprimo was poorly expressed in GC tissues and cells. Mechanically, LINC00467 promoted the methylation and decreased the expression of Reprimo promoter by recruiting DNMT1 in GC cells. Knockdown of LINC00467 diminished the malignant properties of GC cells. Knockdown of LINC00467 reduced tumorigenesis and metastasis of GC cells in vivo. LINC00467 might exert oncogenic effects in GC via Reprimo downregulation by recruiting DNMT1.

Yin Yang 1-induced activation of LINC01133 facilitates the progression of pancreatic cancer by sponging miR-199b-5p to upregulate myelin regulatory factor expression

ABSTRACT Increasing evidence has reported that long non-coding RNA (lncRNA) plays a vital role in the development of pancreatic cancer (PC). However, the function and mechanism of LINC01133 in PC tumorigenesis are still unknown. Herein, we found that LINC01133 was highly expressed in PC tissues and cell lines, and LINC01133 knockdown could block the growth and metastasis of PC cells. Besides, upregulated LINC01133 in PC cells was induced by Yin Yang 1 (YY1). Furthermore, LINC01133 directly targeted miR-199b-5p and promoted cancer malignancy by suppressing miR-199b-5p. It was also discovered that myelin regulatory factor (MYRF) was targeted by miR-199b-5p and positively correlated with LINC01133 expression in PC, and LINC01133 modulated PC progression through miR-199b-5p/MYRF pathway. In conclusion, we demonstrated that YY1-mediated the upregulation of LINC0113 increased MYRF expression by sponging miR-199b-5p, resulting in the accelerated development of PC. These findings might offer a novel insight into the development of efficient therapeutics for PC patients.

Long intergenic non-protein-coding RNA 467 promotes tumor progression and angiogenesis via the microRNA-128-3p/vascular endothelial growth factor C axis in colorectal cancer

Long non-coding RNAs (lncRNAs) are important regulators and biomarkers of tumorigenesis and tumor metastasis. Long intergenic non-protein-coding RNA 467 (LINC00467) is associated with various cancers. However, the role and mechanism of LINC00467 in colorectal cancer (CRC) promotion are poorly understood. This study aimed to present new details of LINC00467 in the progression of CRC. Reverse transcription–polymerase chain reaction demonstrated that the expression level of LINC00467 in CRC tissues and cell lines was significantly upregulated, which was closely related to the clinical features of CRC. Cell and animal studies showed that the downregulation of LINC00467 expression in CRC cells significantly inhibited cell proliferation, metastasis, and angiogenesis. Moreover, the overexpression of LINC00467 accelerated CRC promotion. Bioinformatics analysis and luciferase reporter assay confirmed that LINC00467 binds to miR-128-3p. Rescue experiments manifested that decreased miR-128-3p level reversed CRC cell inhibition by silencing LINC00467. Furthermore, vascular endothelial growth factor C (VEGFC) was identified as a target of miR-128-3p that could reverse the inhibition of cell growth that is mediated by miR-128-3p. Altogether, our results showed that LINC00467 contributes to CRC progression and angiogenesis via the miR-128-3p/VEGFC axis. Our findings expand the understanding of the mechanisms underlying CRC and suggest potential targets for clinical strategies against CRC.

Role of LINC01133 in Osteogenic Differentiation of Dental Pulp Stem Cells by Targeting miR-199b-5p.

Recently, increasing attention has been paid to the function of long non-coding RNAs (lncRNAs) in osteogenic differentiation (OD) of dental pulp stem cells (DPSCs). LINC01133 was reported to have a close relationship with tumorigenesis for multiple cancers, but no study has yet explored the role of LINC01133 in modulating OD of DPSCs. Alizarin red S (ARS) staining and alkaline phosphatase (ALP) staining were perfomed to assess the OD potential of DPSCs. Osteogenic markers including runt-related transcription factor 2 (RUNX2), osterix (OSX) and ALP expression levels in DPSCs were monitored by qRT-PCR and Western blot before and after cell transfection. Luciferase reporter gene assay detected the relationship between LINC01133 and miR-199b-5p. The expression of LINC01133 was low, while miR-199b-5p was increasingly expressed during OD of DPSCs. Overexpression of LINC01133 in DPSCs resulted in decreased expression of RUNX2, OSX, ALP, DSPP and DMP1, whose expression was reversed in DPSCs after transfections of miR-199b-5p overexpression. Co-transfection of pcDNA3.1-LINC01133 and miR-199b-5p mimic led to elevated expression of RUNX2, OSX, ALP, DSPP and DMP1 compared with pcDNA3.1-LINC01133 transfection alone. LINC01133 served as a sponge of miR-199b-5p. AKT3 was verified as a downstream effector of miR-199b-5p in DPSCs. LINC01133 inhibits the OD of DPSCs by upregulating AKT3 via sponging miR-199b-5p, which may act as a potential diagnostic biomarker for dentin regeneration in the dental pulp.

LINC00665 interacts with BACH1 to activate Wnt1 and mediates the M2 polarization of tumor-associated macrophages in GC

Gastric cancer (GC) remains one of the prevalent causes of cancer-related deaths globally. Long non-coding RNAs (lncRNAs) have been associated with different cancers. The polarization of macrophages towards the M2 (alternatively activated) phenotype promotes immunologic tolerance and can induce gastric tumorigenesis. Thus far, lncRNAs have been shown to modulate the differentiation of immune cells. Here, we investigated the biological effects of LINC00665 on the progression of GC and explored the mechanisms underlying its ability to mediate the polarization of macrophages towards the M2 phenotype. We report that the levels of LINC00665 were increased in GC tissues. Furthermore, this increase in LINC00665 expression could be associated with decreased overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS). Using cell-based macrophage polarization models, we demonstrated that LINC00665 upregulation in GC cells facilitated the polarization of macrophages towards the M2 but not M1 (classically activated) phenotype. Furthermore, the loss of LINC00665 prevented the M2 polarization of macrophages. Mechanically, we identified that Wnt1 was the downstream target of LINC00665. Additionally, LINC00665 could directly interact with the transcription factor BTB domain and CNC homology 1 (BACH1). The interaction between LINC00665 and BACH1 resulted in the activation and binding of BACH1 to the Wnt1 promoters. Furthermore, BACH1 silencing could inhibit GC progression, which highlighted a crucial role for BACH1 in LINC00665-mediated Wnt1 activation. In addition, genetic Wnt1 overexpression effectively abolished the repression of Wnt signaling after BACH1 depletion and mediated GC development by supporting M2 macrophage polarization. In conclusion, we report that LINC00665 modulates M2 macrophage polarization and suggest that it may facilitate macrophage-dependent GC progression.

Abnormal pattern of vitamin D receptor-associated genes and lncRNAs in patients with bipolar disorder

BackgroundBipolar disorder (BD) is a multifactorial condition. Several signaling pathways affect development of this disorder. With the purpose of exploring the role of vitamin D receptor (VDR) signaling in this disorder, we measured expression of selected mRNA coding genes and long non-coding RNAs (lncRNAs) in this pathway in patients versus normal subjects.MethodsWe measured expression of VDR-associated lncRNAs and mRNAs (SNHG6, MALAT1, Linc00511, Linc00346, VDR and CYP27B1) in the peripheral blood of BD patients vs. healthy individuals.ResultsExpression of SNHG6 was significantly higher in cases vs. controls (Posterior beta = 1.29, P value < 0.0001. Subgroup analysis by sex revealed significant results in both subgroups (P value < 0.0001 and P value = 0.023 for males and females, respectively). Expression of CYP27B1 was up-regulated in cases vs. controls (Posterior beta = 0.415, P < 0.0001). Such pattern was also detected among males (P < 0.0001), but not females (P = 0.419). Similarly, MALAT1 and Linc00346 were up-regulated in total cases vs. controls (Posterior beta = 0.694, P < 0.0001 and Posterior beta = 0.4, P = 0.012, respectively) and in male cases compared with male controls (Posterior beta = 0.712, P < 0.0001 and Posterior beta = 0.41, P value = 0.038, respectively). Expression of VDR was up-regulated in total cases compared with controls (Posterior beta = 0.683, P value = 0.001). Finally, expression of Linc00511 was not different between groups. MALAT1, SNHG6, CYP27B1, VDR and Linc00346 had AUC values of 0.95, 0.94, 0.91, 0.85 and 0.83 in differentiation of male patients from controls, respectively.ConclusionThe current study suggests VDR-associated genes as possible markers for BD.

LINC00662 Promotes Proliferation and Invasion and Inhibits Apoptosis of Glioma Cells Through miR-483-3p/SOX3 Axis.

LINC00662 plays a prominent role in the carcinogenesis and progression of diverse cancers. However, its biological functions in glioma are still unclear. LINC00662 expression in glioma tissue samples and cell lines was examined by quantitative real-time polymerase chain reaction. The correlation between LINC00662 expression and the clinical characteristics of 50 patients with glioma was analyzed. LINC00662 knockdown and overexpression cell lines were constructed, and the effects of LINC00662 on the proliferation, invasion, and apoptosis of glioma cells were evaluated by cell counting kit-8, 5-ethynyl-2'-deoxyuridine, Transwell, and flow cytometry assays, respectively. Besides, the relationships among LINC00662, miR-483-3p, and sex-determining region Y-box 3 (SOX3) were assessed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Western blot was used to detect the regulatory effects of LINC00662 and miR-483-3p on SOX3 expression in glioma cells. LINC00662 expression level was elevated in glioma tissues and cell lines compared to that in normal tissues and cell lines. LINC00662 high expression was associated with the adverse prognosis of patients with glioma. Knockdown of LINC00662 repressed the proliferation and invasion of glioma cells, and promoted apoptosis. Additionally, it was revealed that LINC00662 acted as the molecular sponge of miR-483-3p, and SOX3 was verified as a direct target of miR-483-3p. The inhibition of miR-483-3p expression and SOX3 overexpression reversed the biological effects of LINC00662 knockdown on glioma cells. This study reports the key regulatory role of LINC00662/miR-483-3p/SOX3 axis in the tumorigenesis and progression of glioma, bringing novel insights into the underlying mechanisms of glioma.

Mechanism Analysis of LINC00665 and Its Peptides CIP2A-BP in Hepatocellular Carcinoma

Background: More and more studies show that long non-coding RNAs (lncRNAs) have miniature open reading frames that can be translated into short peptides. Here, we identify the long non-coding gene LINC00665 and its short peptides (CIP2A-BP) in hepatocellular carcinoma (HCC) and explore how they contribute to HCC progression. Materials and methods: First, GSE101728 data were acquired through the Gene Expression Omnibus for identification of differentially expressed genes (DEGs), and gene set enrichment analysis (GSEA) was conducted to find enriched biological pathways. Then, further bioinformatics analysis was carried out on the screened long non-coding genes, and LINC00665 expression was detected in HCC and normal liver samples. The relations between LINC00665 expression, HCC prognosis, and clinical characteristics were studied. Receiver operating characteristic (ROC) analysis was also applied to verify the LINC00665 prediction in HCC prognosis. In addition, pertinent experiments on LINC00665 and CIP2A-BP were also carried out to explore their roles in the progression of HCC. Results: As a result, we screened out 332 DEGs in total, including 130 upregulated and 202 downregulated DEGs. These DEGs were mainly enriched in posttranscriptional regulation of gene expression, RNA processing, nucleolus, and gene silencing biological pathways. In addition, we found that LINC00665 was increased in HCC samples, which substantially indicated its poor prognosis. Compared with normal tissues, LINC00665 had higher expression in the pathological stages III and IV, tumor-free groups, people no more than 60 years old, and stages T3, T4, N0, N1, and M1. ROC curve indicated that the variable INC00665 had certain accuracy in predicting overall survival (OS). Moreover, in functional experiments, LINC00665 knockdown could significantly decrease HCC cell proliferation, migration, and invasion, while overexpressed CIP2A-BP could markedly increase HCC cell proliferation, invasion, and migration. Conclusion: Our findings not only disclose a unique mechanism by which CIP2A-BP encoded by LINC00665 promotes HCC carcinogenesis but suggest that these long non-coding genes and short peptides could be used as biomarkers for HCC diagnosis and prognosis and new targets for HCC therapy.

LINC00520: A Potential Diagnostic and Prognostic Biomarker in Cancer.

Long non-coding RNA (lncRNA) is important in the study of cancer mechanisms. LINC00520 is located on human chromosome 14q22.3 and is a highly conserved long non-coding RNA. LINC00520 is widely expressed in various tissues. The expression of LINC00520 is regulated by transcription factors such as Sp1, TFAP4, and STAT3. The high expression of LINC00520 is significantly related to the risk of 11 cancers. LINC00520 can competitively bind 10 miRNAs to promote tumor cell proliferation, invasion, and migration. In addition, LINC00520 is involved in the regulation of P13K/AKT and JAK/STAT signaling pathways. The expression of LINC00520 is significantly related to the clinicopathological characteristics and prognosis of tumor patients and is also related to the sensitivity of HNSCC to radiotherapy. Here, this article summarizes the abnormal expression pattern of LINC00520 in cancer and its potential molecular regulation mechanism and points out that LINC00520 can be used as a potential biomarker for cancer diagnosis, prognosis, and treatment.

LINC00958/miR-627 signal axis regulates the proliferation, migration, and invasion of thyroid papillary carcinoma cells by TRIM44.

Papillary thyroid cancer (PTC) has attracted much attention due to its high morbidity and severe metastasis. Long noncoding RNA ENST00000504230 (LncRNA ENST00000504230, known as LINC00958) was overexpressed in many cancers and associated with cancer development. However, its underlying mechanism in PTC remains unclear. PTC tissues and corresponding adjacent tissues were collected for measuring the expression of LINC00958 and miR-627. MiR-627 and TRIM44 expressions were measured in in vitro cultured PTC cell lines (B-cpap and IHH4 cells) transfected with sh-LINC00958 or miR-627 mimic using RT-qPCR and western blot. Cell proliferation, migration, and invasion were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and Transwell assays, respectively. Dual-luciferase reporter assay was performed to evaluate the target association between miR-627 and TRIM44. LINC00958 was up-regulated in PTC tissues and cells, while the expression of miR-627 was lowly expressed. Knockdown of LINC00958 inhibited the proliferation, migration, and invasion by elevating miR-627 expression in PTC cells. TRIM44 was confirmed as a target of miR-627. Overexpression of miR-627 in PTC inhibited the proliferation, migration, and invasion by down-regulating the expression of TRIM44. LINC00958 promoted proliferation, migration, and invasion in PTC by down-regulating miR-627 and activating TRIM44, indicating the potential therapeutic effect of LINC00958 on PTC.

LINC00518 affects the proliferation, invasion and migration of cutaneous malignant melanoma cells via miR-526b-3p/EIF5A2 axis

To investigate the mechanism of LINC00518 affecting the proliferation, invasion, and migration of cutaneous malignant melanoma (CMM) cells via miR-526b-3p/EIF5A2 axis. qRT-PCR was performed to measure the expression of LINC00518, miR-526b-3p, and EIF5A2 in CMM tissues from 40 patients. Si-LINC00518, pcDNA-LINC00518, miR-526b-3p mimic, miR-526b-3p inhibitor, si-EIF5A2, and their corresponding negative controls were transfected alone or co-transfected into CMM cells A375 and A2058. The expression of LINC00518, miR-526b-3p and EIF5A2 in A375 and A2058 cells was measured. Cell proliferation was tested by CCK-8 assay and EdU assay. Cell invasion and migration were detected by Transwell and scratch tests, respectively. The binding between LINC00518 and miR-526b-3p, and the binding between miR-526b-3p and EIF5A2 were verified by dual-luciferase reporter and RNA pull-down assays. LINC00518 and EIF5A2 were up-regulated and miR-526b-3p was down-regulated in CMM tissues and cells. CMM patients with highly expressed LINC00518 showed decreased survival time than those with lowly expressed LINC00518. Transfection of si-LINC00518, miR-526b-5p mimic or si-EIF5A2 weakened the proliferative, migratory, and invasive abilities of melanoma cells, while transfection of miR-526b-5p inhibitor or pcDNA-LINC00518 enhanced the progression of melanoma cells. Moreover, the proliferative, migratory, and invasive potentials of melanoma cells were decreased after co-transfection of si-EIF5A2 and pcDNA-LINC00518 compared with cells transfected with pcDNA-LINC00518 alone. LINC00518 bound to miR-526b-3p and miR-526b-3p targeted EIF5A2. LINC00518 negatively regulated miR-526b-3p expression but positively regulated EIF5A2. Furthermore, EIF5A2 expression was negatively associated with miR-526b-3p expression. LINC00518 encourages CMM through the miR-526b-3p/EIF5A2 axis in terms of cell proliferation, invasion, and migration.