LINC00152 Expression Research Articles

Long non‑coding RNA LINC00460 contributes as a potential prognostic biomarker through its oncogenic role with ANXA2 in colorectal polyps.

Long intergenic non-coding RNA 460 (LINC00460) as a potential oncogene and Annexin A2 (ANXA2) as a promoter in different cancer progression processes was considered. A significant relationship between the LINC00460 and ANXA2 has been recently discovered in colorectal cancer (CRC). Therefore, defining molecular biomarkers accompanied by lesion histopathologic features can be a suggestive prognostic biomarker in precancerous polyps. This study aimed to investigate the elusive expression pattern of ANXA2 and LINC00460 in polyps. The construction of the co-expression and correlation network of LINC00460 and ANXA2 was plotted. LINC00460 and ANXA2 expression in 40 colon polyps was quantified by reverse transcription-real-time polymerase chain reaction. The receiver operating characteristic (ROC) curve was designed for distinguishing the high-risk precancerous lesion from the low-risk. Further, bioinformatics analysis was applied to find the shared MicroRNA-Interaction-Targets (MITs) between ANXA2 and LINC00460, and the associated pathways. ANXA2 has a high co-expression rank with LINC00460 in the lncHUB database. Overexpression of ANXA2 and LINC00460 was distinguished in advanced adenoma polyps compared to the adjacent normal samples. The estimated AUC for ANXA2 and LINC00460 was 0.88 - 0.85 with 93%-90% sensitivity and 81%-70% specificity. In addition, eight MITs were shared between ANXA2 and LINC00460. Enrichment analysis detected several GO terms and pathways, including HIF-1α associated with cancer development. In conclusion, the expression of the ANXA2 and LINC00460 were significantly elevated in pre-cancerous polyps, especially in high-risk adenomas. Collectively, ANXA2 and LINC00460 may be administered as potential prognostic biomarkers in patients with a precancerous large intestine lesion as an alarming issue.

Abstract 1405: Long non-coding RNA LINC01614 augments papillary thyroid cancer cell phenotype

Abstract Papillary thyroid cancer (PTC) accounts for the vast majority of thyroid cancer cases and despite high survival rates, disease recurrence and metastasis remain prominent issues. Therefore, there is a need to identify potential molecular markers associated with PTC that aid in early diagnosis, prognosis, and that may serve as therapeutic targets. One area of focus for cancer study is trending towards the epigenome and its functional regulators. The largest subclass of RNA molecules in the human genome consists of long intergenic non-coding RNAs (lincRNAs) with many of their functions yet to be identified. Evidence supports their roles in the regulation of gene expression, as these molecules can act as scaffolds for RNA and protein localization as well as act as molecular “sponges” for binding to and inhibiting action of specific miRNAs. Recently, long non-coding RNA molecules have been demonstrated to play roles in both the development and progression of cancer, deeming them as both attractive and specific biomarkers and/or therapeutic targets for study. Data from our patient sample biobank identified LINC01614 as being significantly upregulated (~12 fold increase) in PTC, when compared to normal, matched thyroid tissue. There was also ~30 fold increase in LINC01614 expression in male PTC, compared to ~5.5 fold increase in female PTC, highlighting a potential sex correlation for study. Thus, we are studying LINC01614 as a potential PTC biomarker. Functional analysis of LINC01614 in vitro found it to be upregulated in various thyroid cancer cell lines, specifically two PTC cell lines: TPC1 (~5 fold; RET/PTC rearrangement; female) and K1 (~2 fold; BRAFV600E; male) when compared to the immortalized “normal” thyroid cell line (Nthy-ori-3-1). To establish a phenotype for LINC01614 expression, we utilized the CRISPRi technique to knockdown expression of this lincRNA in both TPC1 and K1. Knockdown resulted in decreased healing capacity (~20% for both), clonogenicity (~50% and ~34%, respectively), and proliferation (~55% and ~45%, respectively) in both the TPC1 and K1 PTC cell lines. Studies are underway to further assess migration, invasion, and morphology in both cell lines as well as studies to elucidate potential protein interactions and mechanisms of action of LINC01614 in PTC. Studying lincRNAs and their regulatory roles in cancer cell function can aid in the identification of various molecular markers for therapeutic intervention. Elucidation of how these molecules impact PTC development and progression is a promising avenue of exploration. Citation Format: Danielle Quaranto, Michelle Carnazza, Nicole DeSouza, Sina Dadafarin, Augustine Moscatello, Raj Tiwari, Jan Geliebter. Long non-coding RNA LINC01614 augments papillary thyroid cancer cell phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1405.

Long non-coding RNA LINC00958 and microRNA miR-627-5p provide candidate diagnostic biomarker and participate tumor progression in laryngeal squamous cell carcinoma: a retrospective study.

Laryngeal squamous cell carcinoma (LSCC) is known for its high morbidity and mortality. Long non-coding RNAs and miRNA have been found to play important roles in cancer progression. However, the roles of LINC00958 and miR-627-5p in LSCC and their mechanisms remain unclear. Therefore, it is important to explore its role in LSCC. The results of this study show that the expression of LINC00958 was significantly increased (p<0.001), but the expression of miR-627-5p was significantly decreased in LSCC serum specimens and cell lines (p<0.001). Silencing LINC00958 or overexpression of miR-627-5p could inhibit the proliferation (p<0.05) and migration (p<0.01) of LSCC cells. According to the results of dual luciferase reporter assay, it was known that LINC00958 could target miR-627-5p (p<0.01). ROC experiment results showed that LINC00958 was used to distinguish LSCC patients from healthy controls, OSCC patients from healthy controls and LSCC patients from OSCC patients, and the areas under the curve (AUC) were 0.970, 0.809 and 0.811, respectively. Meanwhile, we found that serum miR-627-5p could also be used to distinguish LSCC patients from healthy controls, oral squamous cell carcinoma (OSCC) patients from healthy controls, and LSCC patients from OSCC patients, with the AUC of 0.975, 0.870, and 0.800, respectively. Pearson analysis showed that the expression level of LNIC00958 was negatively correlated with the expression level of miR-627-5p (r= -0.725, p<0.001). Overall, The results of this study show that LINC00958 and miR-627-5p may be used as new diagnostic markers for LSCC. In addition, LINC00958/miR-627-5p axis opens a new way for the diagnosis and treatment of LSCC.

Dermoscopic features associated with 3-GEP PLA: LINC00518, PRAME, and TERT expression in suspicious pigmented lesions.

Utilization of dermoscopy and novel molecular triage technologies augments visual triage of pigmented skin lesions, promoting early detection of melanoma. One emerging in vivo genomic test, 3-GEP pigmented lesion assay (3-GEP PLA) aids in pigmented lesion triage by noninvasively detecting the presence of three genes associated with melanoma: LINC00518, PRAME, and TERT. The purpose of our retrospective case-control study was to identify dermoscopic features uniquely associated with the presence of LINC00518, PRAME, or TERT in the stratum corneum as determined by 3-GEP PLA testing. Images of suspicious pigmented lesions that had undergone 3-GEP PLA testing and received a definitive positive or negative result (n = 393) were evaluated for the presence of specific clinical and dermoscopic features associated with melanoma. We found that asymmetry of color was a significant predictor for PRAME expression (Odds Ratio (OR) 5.5, 95% Confidence Interval (CI) 1.6-34.5, p = 0.004), blue color and negative pigment network were significant predictors for LINC00518 expression (adjusted OR 2.7, 95% CI 1.2-5.5, p = 0.014 and adjusted OR 5.4, 95% CI 1.6-16.9, p = 0.010, respectively), and atypical polymorphous vessels present in a pigmented skin lesion were a significant predictor for TERT promoter mutations (OR 5.8, 95% CI 1.3-23.4, p = 0.022). The results presented suggest a hierarchy in the significance of these dermoscopic features and may help guide evaluation and management of pigmented skin lesions.

LINC01116 modulates EMT process via binding with AGO1 mRNA in oesophageal squamous cell carcinoma

Recent researches have uncovered that long non-coding RNAs (lncRNAs) are closely correlated with the development of different diseases, while biological functions and hidden molecular mechanisms of antisense lncRNAs in oesophageal squamous cell carcinoma (OSCC) remain unclear. Here, we identified upregulation of LINC01116 in RNA sequencing data, online database, and in OSCC and intraepithelial neoplasia (IEN) specimens. Functionally, LINC01116 facilitates OSCC advancement and metastasis in vitro and vivo. Mechanistically, elevated expression of LINC01116 in OSCC cells other than tumor stroma and cytoplasmic enables it to activate AGO1 expression via complementary binding with AGO1 mRNA to facilitate EMT process of OSCC.

Knockdown of LINC00511 enhances radiosensitivity of lung adenocarcinoma via regulating miR-497-5p/SMAD3

ABSTRACT As the most common histological subtype of primary lung cancer, lung adenocarcinoma (LUAD) causes enormous cancer deaths worldwide. Radiotherapy has been frequently used in LUAD cases, and radiosensitivity is vital for LUAD therapy. This research sought to explore the genetic factors affecting radiosensitivity in LUAD and inner mechanisms. LINC00511, miR-497-5p, and SMAD3 expression in LUAD cells were detected via qRT-PCR and western blot. CCK-8 assays, colony formation, and flow cytometry assays were employed to explore the cell viability, apoptosis, and radiosensitivity in PC-9 and A549 cells. The targeting relationship between LINC00511, miR-497-5p, and SMAD3 was verified by dual luciferase reporter assay. Furthermore, xenograft experiments were performed for the in vivo verification. In conclusion, LINC00511 was overexpressed in LUAD cells, which downregulated downstream miR-497-5p expression and mediately led to SMAD3 activation. LINC00511 downregulation suppressed cell viability while enhanced apoptosis rate in LUAD cells. Also, LINC00511 and SMAD3 were overexpressed, while miR-497-5p was downregulated in LUAD cells exposed to 4Gy irradiation treatment. Moreover, LINC00511 inhibition could block SMAD3 expression and promoted the radiosensitivity both in vitro and in vivo. These findings uncover LINC00511 knockdown promoted miR-497-5p expression and subsequently led to lower SMAD3 level, which enhanced radiosensitivity in LUAD cells. LINC00511/miR-497-5p/SMAD3 axis could be of considerable potential to enhance radiosensitivity in LUAD.

LINC00511 promotes melanoma progression by targeting miR-610/NUCB2.

Long intergenic noncoding RNA 00511 (LINC00511) predicts poor prognosis in various malignancies and functions as an oncogene in distinct malignant tumors. The role of LINC00511 in melanoma progression was assessed. In our research, expression of LINC00511 in melanoma cells was detected by quantitative reverse transcription PCR. Colony formation and CCK8 assays were used to detect cell proliferation. Cell metastasis was evaluated by transwell and wound healing assays. Downstream target of LINC00511 was investigated by luciferase activity assay. As a results, LINC00511 was elevated in melanoma cells and tissues. Loss of LINC00511 decreased cell viability, reduced proliferation, invasion, and migration of melanoma. miR-610 was target of LINC00511, and miR-610 binds to 3'UTR of nucleobindin-2 (NUCB2). Inhibition of miR-610 attenuated LINC00511 deficiency-induced decrease of NUCB2 in melanoma cells. Loss of miR-610 weakened LINC00511 deficiency-induced decrease of cell viability, proliferation, invasion, and migration of melanoma. In conclusion, silence of LINC00511 reduced cell proliferation and metastasis of melanoma through down-regulation of miR-610-mediated NUCB2.

Misexpression of LINC01410, FOSL1, and MAFB in peripheral blood mononuclear cells associated with diabetic nephropathy

AimsCurrently, diabetic nephropathy (DN) is considered the leading cause of the end-stage renal disease (ESRD). However, its specific molecular mechanism is still unclear, and there is still a lack of effective diagnostic and therapeutic methods. MethodA pathway was assumed after bioinformatics analysis of GEO datasets related to individuals with various levels of DN, LINC01410, MAFB, and FOSL1. Then, 46 patients with type 2 diabetes (T2DM) and different levels of albuminuria, and 12 individuals without diabetes, were selected. qPCR was performed to evaluate gene expression. One-way ANOVA followed by Tukey’s -and linear trend tests were performed to analyze gene expression in different stages of the disease. Moreover, receiver operating characteristic (ROC) curves and the correlation between LINC01410, FOSL1, and MAFB were analyzed. ResultsLINC01410, MAFB, and FOSL1 were selected based on bioinformatics analyses. The qPCR results showed that the expression of LINC01410 decreased, and FOSL1 and MAFB increased in micro-and macroalbuminuria groups compared to normoalbuminuria groups (P < 0.05). ROC curves demonstrated a significant diagnostic accuracy of LINC01410, MAFB, and FOSL1 between DN and participants with normoalbuminuria (P < 0.05). Pearson’s correlation analysis revealed a positive association between the expressions of FOSL1 and MAFB (p = 0.01, r = 0.39). However, there was no correlation between LINC01410 with MAFB and FOSL1 (p = 0.23 and p = 0.21, respectively). ConclusionDysregulation of LINC01410, MAFB, and FOSL1 is related to DN. These results may provide new insights into the role of LINC01410, MAFB, and FOSL1 as potential biomarkers in DN.

A systematic review and meta-analysis of long noncoding RNA 00963 expression and prognosis and clinicopathological characteristic in human cancers

Numerous studies have indicated that the aberrant expression of LINC00963 is extensively present in various human tumors, and that dysregulation of LINC00963 is implicated in the initiation and progression of human cancers. In this meta-analysis, data from diverse malignancies were analyzed to determine whether LINC00963 expression levels were associated with clinical prognosis and immune infiltration in pan-cancer. The eligible studies were identified from several electronic databases from the inception to July 2022 through systematic research. LINC00963 expression and survival were estimated using pooled odds ratios and hazard ratios with 95% CI. We used the Kaplan-Meier method and COX analysis for survival analysis. In addition, Spearman's correlation analysis was used to uncover any correlation between LINC00963 and microsatellites instability (MSI), tumor mutational burden (TMB), DNA methyltransferases (DNMTs), immune checkpoint biomarkers, and the related genes of mismatch repair (MMR). Our findings indicated that overexpression of LINC00963 was related to poor overall survival (OS) (HR =1.32, 95% CI, 1.09-1.59, P= 0.004). The TCGA database also found that abnormal expression of LINC00963 was linked to overall survival in various cancers. Moreover, there is an association between LINC00963 expression and MSI, TMB, and MMR in malignancies of various types. The results of this study indicate that LINC00963 may serve as a prognostic biomarker and a therapeutic target for cancer. By using it, cancer diagnoses can be improved, treatment targets discovered, and prognostic questions improved.

Abstract A006: LINC00261 acts as a surrogate biomarker for tumor DNA mutational burden and immunotherapeutic response in lung adenocarcinoma

Abstract Defects in DNA repair allow for the age-dependent accumulation of mutations, which is significantly linked to the age-dependent increase in the development of neoplasia. Our lab has identified the long non-coding RNA LINC00261 as a critical activator of DNA damage signaling whose expression increases with age in normal lung tissue but is lost in the majority of Lung Adenocarcinomas (LUAD). We therefore undertook a mechanistic investigation on the relationship between LINC00261 function in lung and the accumulation of mutations by utilizing expression and mutational load data from The Cancer Genome Atlas, as well as in vitro mechanistic investigation into the functional relationship between LINC00261 and tumor mutational burden (TMB). Here we report (1) the observation of an age-dependent increase in LINC00261 expression in normal lung tissue within the TCGA adjacent non-tumor lung dataset; (2) a significant correlation between TMB and LINC00261 expression, where elevated LINC00261 levels are associated with decreased TMB; (3) LINC00261 effects on TMB were driven primarily by transition mutations, characteristic of defects in nucleotide excision repair. Standard of care treatment for disseminated LUAD often includes systemic platinum-based chemotherapies, including cisplatin, that act by inducing lethal levels of DNA damage. We observed that the presence of LINC00261 in LUAD causes cellular resistance to cisplatin-mediated DNA-damage in vitro. Our results suggest that patients with tumors expressing LINC00261 should be considered for non-platinum based therapeutic strategies. High mutational loads are also associated with the creation of neoantigens, allowing for immune recognition and when combined with PD-L1 expression levels can serve as an indicator for successful immunotherapy. Testing for PD-L1 expression is now standard of care, however exome sequencing to determine TMB is not often pursued outside academic medical centers due to expense, extensive bioinformatic involvement, and difficulty interpreting results. In addition, high levels of TMB does not always confer active neoantigen presentation as MHC Class II genes are often dysregulated in cancer. We therefore sought to determine if LINC00261 can function as a surrogate biomarker for TMB and provide complimentary indications to PD-L1 testing for successful immunotherapeutic response. Reintroduction of ectopic LINC00261 was able to activate expression of MHC Class II genes involved in neoantigen presentation. Conversely, Interferon gamma addition was able to induce endogenous expression of LINC00261 in vitro. Our results suggest there is a mechanistic relationship between LINC00261 expression and functional MHC Class II neoantigen presentation in LUAD. This was supported by observations that LINC00261 expression is significantly correlated to MHC Class II expression within TCGA LUAD cohort. Taken together, our results suggest LINC00261 shows promise as a biomarker of mutational burden and MHC Class II expression. Citation Format: Jonathan Castillo, Tianchun Xue, Mayela Norwood, Samantha Joseph, Crystal N. Marconett. LINC00261 acts as a surrogate biomarker for tumor DNA mutational burden and immunotherapeutic response in lung adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A006.

LINC00963 promotes the malignancy and metastasis of lung adenocarcinoma by stabilizing Zeb1 and exosomes-induced M2 macrophage polarization

BackgroundLong intergenic non-coding RNA 00963 (LINC00963) is an oncogenic lncRNA in human cancers. However, little is known on how it impacts the pathogenesis of lung adenocarcinoma (LUAD).MethodsBiological effects on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were examined by CCK-8, colony formation, EdU incorporation, transwell, and immunofluorescence assays, respectively. Macrophage polarization was evaluated by flow cytometry. Ubiquitination of Zeb1 was examined by co-immunoprecipitation. The location of LINC00963 in LUAD tissues and cell lines was tested by FISH assay. The LINC00963/HNRNPA2B1/Siah1 mRNA complex interaction was verified using RNA pull-down and immunoprecipitation assays. The exact roles of LINC00963 were further validated in metastasis and xenograft models.ResultsHigher LINC00963 expression in LUAD patients positively correlated with shorter overall survival, higher stages, and metastasis. LINC00963 mainly localized in the cytoplasm and aggravated malignant phenotypes of LUAD cells in vitro and metastasis in vivo. Mechanistically, LINC00963 directly interacted HNRNPA2B1 protein to trigger the degradation of Siah1 mRNA, which inhibited the ubiquitination and degradation of Zeb1. Moreover, exosomal LINC00963 derived from LUAD cells induced M2 macrophage polarization and promoted LUAD growth and metastasis.ConclusionBy stabilizing Zeb1 in cancer cells and delivering exosomes to induce M2 macrophage polarization, LINC00963 promoted the malignancy and metastasis of LUAD. Targeting LINC00963 may become a valuable therapeutic target for LUAD.

The Expression of LINC00673 in Colon Cancer and the Melatonin's Effect on Its Expression

Objective: In this study, the cell lines SW620 and DLD-1 which belongs to colon cancer were employed with the aim of observing melatonin's effect on the growth of colon cancer cells and exploring the influence of melatonin about the autophagy of colon cancer. Besides. It uses qRT-PCR to identify LINCRNA00673 (LINC00673) expression in colon cancer and the influence of melatonin on LINC00673 expression.For the purpose of providing a fundamental theory for melatonin in anti-cancer therapy and also presenting as a biomarker for the early detection of colon cancer. Method: 1) Cultivating the colon cancer cell lines SW620 and DLD-1, and subdividing them in accordance with distinct concentrations of melatonin: 0 mM, 1mM, and 2mM, to detect the impact of melatonin for migration and growth of colon cancer cells by Cell Scratch Test and Colony Formation Assay.2) Detecting the expression level of autophagy-related molecules in colon cancer cells in response to melatonin employing Western Blot Assay. 3) Utilizing QT-PCR, extract RNA from two groups of cells and detect the expression of LINC00673 and LINC00673 following melatonin treatment. Result: 1) The Cell Scratch test and Colony Formation Assay indicated that compared with the normal group, the scratch healing of SW620 cells and DLD-1 cells decreased. Furthermore, following melatonin administration, the number of cell colonies decreased. And the results are statistically significant. 2) Western blotting results illustrated that after the interferon of melatonin, the expression level of the autophagy-related molecule Beclin-1 increased significantly, whereas the expression of P62 decreased. 3) QT-PCR results demonstrated that the expression of LINC00673 in colon cancer cells SW620 and DLD-1 was significantly increased. Moreover, melatonin had an inhibiting effect on it. Conclusion: These in vitro experiments managed to prove that melatonin possesses a powerful anti-colon cancer effect and can inhibit the growth and spread of colon cancer. Western blotting indicated that melatonin can inhibit colon cancer through autophagy. Besides which, it is discovered that melatonin may exert its anticancer effect by influencing LINC00673.

The Role of Long Non-Coding RNA LINC00467 in Gastric Carcinoma: High Proliferation, Migration and Autophagy

The goal of this study is to investigate the role of long non-coding RNA LINC00467 in gastric carcinoma (GC) progression. Differential expressions of LINC00467 in GC samples were detected. By analyzing the follow-up data of recruited GC patients, the influence of LINC00467 on their prognosis was assessed. After knockdown of LINC00467 in SGC7901 and MKN45 cells, cell autophagy was examined by GFP-LC3 puncta assay and Western blot analyses on autophagy-associated genes. Additionally, cell growth and migration were assessed using cell counting kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), and transwell assays. The connection between LINC00467 and miR-18a-5p was studied through a luciferase assay and Pearson correlation analysis. Increased expression of LINC00467 was observed in GC samples and its elevated levels predicted a poor outcome for GC patients. The suppression of LINC00467 reduced the proliferative and migratory capacities of SGC7901 and MKN45 cells. LINC00467 level was closely linked to autophagy activity in GC. The level of miR-18a-5p was decreased in GC tissues and had an inverse correlation with LINC00467, which was established as the target of miR-18a-5p. Upregulated LINC00467 induces growth, metastasis and autophagy activity in GC through negatively regulating miR-18a-5p level, thus leading to the poor prognosis in GC patients.

Linc00511 Knockdown Inhibits Lung Cancer Progression by Regulating miR-16-5p/MMP11.

Lung cancer (LC) is a malignant tumor that extremely impairs people. According to numerous studies, long non-coding RNA (lncRNA) was inextricably involved in the advancement of LC. The work aspired to identify linc00511 expression in LC and to dig for the underlying mechanisms linc00511 regulated LC progression. Experimental outcomes revealed that linc00511 was obviously upregulated in LC, and linc00511 knockdown significantly impaired the malignant phenotype of LC cells in vitro. For an in-depth study on the contribution of linc00511 to LC advancement, it was disclosed that miR-16-5p had binding sites to the sequence of linc00511, which also inversely affected linc00511 expression in LC. Further experimental data demonstrated that miR-16-5p directly and negatively targeted matrix metallopeptidase 11 (MMP11). Also, rescue experiments displayed that miR-16-5p inhibition or MMP11 overexpressing offset the suppressive impacts of linc00511 silencing on LC progression. To sum up, our findings indicated that linc00511 performed a crucial role in facilitating LC progression, and mechanistic studies demonstrated that linc00511 aggravated LC progression via targeting the miR-16-5p/MMP11 axis.

LINC00460 Facilitates Cell Proliferation and Inhibits Ferroptosis in Breast Cancer Through the miR-320a/MAL2 Axis.

Background: Emerging evidence suggests that long noncoding RNAs (lncRNAs) play an important role in the progression of multiple human cancers including breast cancer. In this study, we aimed to research novel functions of long intergenic noncoding RNA 460 (LINC00460) on cell proliferation and ferroptosis in breast cancer. Method: UALCAN, TANRIC, and GSE16446 data were used to analyze the expression of LINC00460 in breast cancer tissues. Furthermore, real-time quantitative PCR, western blot, cell proliferation assay, iron assay, and malondialdehyde (MDA) assay were applied to detect the function and mechanism of particular molecules. Results: The LINC00460 expression was significantly increased in breast cancer tissues compared with normal tissues. Importantly, patients with high LINC00460 expression showed a longer overall survival rate. LINC00460 knockdown markedly suppressed the proliferation of breast cancer cells and promoted ferroptosis. Mechanistic analysis revealed that LINC00460 promoted myelin and lymphocyte protein 2 (MAL2) expression by sponging miR-320a. Moreover, both miR-320a knockdown and MAL2 overexpression could reverse the effects of LINC00460 silencing on cell proliferation and ferroptosis. Conclusions: In summary, our results reveal an alternative mechanism by which breast cancer cells can acquire resistance to ferroptosis via the LINC00460/miR-320a/MAL2 axis.

Long Non-coding RNA LINC00473 Promotes Breast Cancer Progression via miR-424-5p/CCNE1 Pathway.

There has been a large increase in the incidence of breast cancer (BC) among women. LINC00473 is a cancer-related lncRNA, participating in the progression of many cancers, but its role in the progression of BC awaits more elaboration. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify LINC00473, miR-424-5p, and cyclin E1 (CCNE1) mRNA expression levels in BC tissues and cells. Cell counting kit-8 (CCK-8) assay was employed to detect the cell viability; the cell migration and invasion abilities were evaluated by the Transwell assay. Western blot and immunohistochemistry (IHC) were adopted to study CCNE1 protein expression; dual-luciferase reporter assay was performed to clarify the targeting relationships among LINC00473, miR-424-5p, and CCNE1. LINC00473 expression was elevated in BC tissues and cell lines, which was associated with lymph node metastasis and higher clinical stage of the patients with BC. LINC00473 proved to be a molecular sponge for miR-424-5p; LINC00473 knockdown impeded the growth, migration, invasion, and epithelial-mesenchymal transition of BC cells, while these effects were abolished by miR-424-5p inhibitors; miR-424-5p targeted CCNE1 to restrain its expression. LINC00473 positively regulated CCNE1 expression, and CCNE1 restoration counteracted the effects induced by LINC00473 knockdown in BC cells. LINC00473 facilitates the progression of BC through miR-424-5p/CCNE1 axis.

The clinical prognostic value of lncRNA LINC00473 in cancer patients: A meta-analysis.

LINC00473 is a promising long non-coding RNA. There is increasing evidence that SNHG7 is abnormally expressed in various tumors and is associated with cancer prognosis. However, identification of the effect of long non-coding RNA LINC00473 in tumors remains necessary. Up to August 15, 2021, we searched electronic databases, including PubMed, Cochrane Library, EMBASE, Medline, and Web of Science. The results were evaluated by pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs). There weres 13 included literature totaling cancer patients involved in this meta-analysis. The aggregated results revealed that high expression of LINC00473 was significantly associated with unfavorable overall survival (HR = 1.66, 95% CI: 1.48-1.86, P < .00001), disease-free survival (HR = 1.59, 95% CI: 1.09-2.32, P = .02) in a variety of cancers. Additionally, increased LINC00473 expression was also correlated with tumor node metastasis stage ((III/IV vs I/II) OR = 4.67, 95% CI = 3.11-7.02, P < .00001), differentiation ((poor/moderately vs well) OR = 3.25, 95% CI = 1.41-7.50, P = .006), tumor size ((larger vs smaller) OR = 2.49, 95% CI = 1.26-4.91, P = .03), and lymph node metastasis ((positive vs negative) OR = 3.10, 95% CI = 2.13-4.51, P = .008) in patients with cancers. Besides, the Gene Expression Profiling Interactive Analysis dataset evaluated that LINC00473 was upregulated in a variety of tumors and predicted worse prognosis. Our results of this meta-analysis demonstrated that high LINC00473 expression may become a potential target for predicting prognosis of human cancers.

IGF2BP2 enhances LincRNA01116 stability via m6 A: A potential biomarker and therapeutic target for patients with pre-eclampsia.

Pre-eclampsia (PE) is a serious complication in pregnant women characterized by failure of placental remodeling and is one of the primary causes of changes in the placental structure and function. The aberrant expression of long noncoding RNA is associated with the occurrence and progression of PE. This study found that linc01116 expression was significantly downregulated in PE patients and was related to poor uterine spiral artery remodeling. Knockdown of linc01116 remarkably decreased the angiogenesis of trophoblast cells in vitro and in vivo. Mechanistically, IGF2BP2 regulated linc01116 RNA stability via m6 A methylation. Bioinformatics and other experiments further revealed that linc01116 upregulates AAMP expression by adsorbing miR-210-3p in trophoblast cells. In conclusion, this study revealed the critical role of linc01116 in regulating trophoblast angiogenesis. Furthermore, the study provides new clues for detecting placental pathology in PE.

LINC00460 Promotes Cutaneous Squamous Cell Carcinoma Progression Through Stabilizing ELAVL1 Protein

Long intergenic noncoding ribonucleic acid (lncRNA) 460 is reportedly associated with carcinogenesis and progression in various types of cancer. However, the mechanisms underlying its action in cutaneous squamous cell carcinoma (CSCC) remain unclear. LINC00460 mRNA expression was analysed using data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Cell growth, migration, and invasion were evaluated using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), transwell migration and invasion assays after inducing LINC00460 knockdown. A xenograft tumour model was used to determine the effects of LINC00460 on tumour growth and metastasis in vivo. To examine the interaction between LINC00460 and ELAVL1, RNA pulldown and RNA immunoprecipitation assays were performed. LINC00460 was found to be significantly upregulated in CSCC tissues and cell lines. Functionally, LINC00460 knockdown inhibited cell proliferation, migration, and invasion in vitro. Consistent with this, when LINC00460 expression decreased, CSCC tumorigenesis and metastasis in vivo were inhibited. Mechanistically, LINC00460 binds to embryonic lethal abnormal vision like RNA binding protein 1 (ELAVL1) and enhances its stability by inhibiting the β-transducin repeats-containing protein (β-TrCP)-mediated ubiquitination of ELAVL1. Moreover, the effect of LINC00460 silencing on the proliferation, migration, and invasion of CSCC cells could be reversed by overexpressing ELAVL1. Our findings demonstrated that LINC00460 plays a critical role in regulating ELAVL1 function. This highlights the potential targets for the clinical diagnosis and treatment of CSCC.

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.