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Silencing of Long Non-Coding RNA LINC01106 Suppresses the Proliferation, Migration and Invasion of Endometrial Cancer Cells Through Regulating the miR-449a/MET Axis

ABSTRACT: Purpose Endometrial cancer (EC) is an aggressive tumor in females and the development of EC is considered to regulate by some long non-coding RNAs (lncRNAs). Therefore, this study aimed to investigate the regulatory mechanism of lncRNA LINC01106 on EC. Methods The expression of lncRNA LINC01106, miR-449a and MET in EC tissues and cells was detected by qRT-PCR. Through MTT, wound healing and transwell invasion assays, the proliferation, migration and invasion of EC cells were detected, respectively. The xenograft tumor model was constructed in nude mice to confirm the inhibiting effect of LINC01106 knockdown on EC in vivo. The interactions between miR-449a and LINC01106/MET were predicted by Starbase/Targetscan software and verified by the dual-luciferase reporter assay or RNA immunoprecipitation assay. Western blot assay was performed to determine the protein level of MET. Results LncRNA LINC01106 expression was highly up-regulated in EC tissues and cells. The proliferation, migration and invasion of EC cells in vitro were inhibited by the transfection of sh-LINC01106. The growth of tumor xenograft was suppressed by injection of sh-LINC01106. MiR-449a was a target of LINC01106and was negatively modulated by LINC01106. MiR-449a overexpression suppressed the proliferation, migration and invasion of EC cells. In addition, MET was identified as a target gene of miR-449a. Both the high expression of miR-449a and low expression of MET reversed the inhibiting effects of LINC01106 knockdown on Ishikawa cells. Conclusion Silencing of LINC01106 inhibits the occurrence and development of EC via regulating the miR-449a/MET axis. This study provides a possible therapeutic strategy for EC.

SUBMITTER: Gao X

PROVIDER: S-EPMC7532893 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe pivotal roles of long noncoding RNAs (lncRNAs) in the realm of cancer biology, inclusive of bladder cancer (BCa), have been substantiated through various studies. Remarkably, RNA methylation, especially m6A modification, has demonstrated its influence on both coding and noncoding RNAs. Nonetheless, the explicit impact of RNA methylation on lncRNAs and its subsequent contribution to the progression of BCa remains to be elucidated.MethodsIn the present investigation, we scrutinized the expression and m6A methylation status of LINC01106, employing quantitative real-time PCR (qRT-PCR) and methylated RNA immunoprecipitation (MeRIP)-qPCR. To decipher the regulatory mechanism underpinning LINC01106, we utilized RNA immunoprecipitation (RIP)-qPCR, methylated RNA immunoprecipitation (MeRIP) assays, and bioinformatic analysis. Furthermore, the CRISPR/dCas13b-METTL3-METTL14 system was implemented to probe the function of LINC01106.ResultsThe findings of our study indicated that LINC01106 is under expressed and exhibits diminished m6A methylation levels in BCa tissues when compared those of normal controls. A diminished expression of LINC01106 was associated with a less favorable prognosis in BCa patients. Intriguingly, CRISPR-mediated hypermethylation of LINC01106, facilitated by dCas13b-M3-M14, abolished the malignant phenotype of the BCa cells, an effect that could be inverted by Disabled-1 (DAB1) knockdown. From a mechanistic standpoint, we identified an m6A modification site on LINC01106 and highlighted YTHDC1 as a potential reader protein implicated in this process. Additionally, a positive correlation between DAB1 and LINC01106 expression was observed, with miR-3148 potentially acting as a mediator in this relationship.ConclusionsIn summary, our research unveils a suppressive regulatory role of the LINC01106/miR-3148/DAB1 axis in the progression of BCa and underscores the YTHDC1-mediated m6A modification mechanism in regards to LINC01106. These revelations propose a new therapeutic target for the management of BCa.

Project description:BackgroundEmerging evidence shows that abnormal expression of long non-coding RNA is involved in the occurrence and development of various tumors. LncRNA MONC is abnormally expressed in head and neck squamous cell carcinoma, lung cancer, colorectal cancer, and acute megakaryocytic leukemia, but the biological function and potential regulatory mechanism of MONC in endometrial cancer stem cells (ECSCs) and endometrial cancer cells (ECCs) have not been studied. In this study, we aimed to explore the tumor suppressive effect and mechanism of MONC in regulating ECSCs and ECCs.MethodsWe used qRT-PCR to detect the expression of MONC, miR-636 and GLCE in normal human endometrial tissues and endometrial carcinoma (EC) tissues. Luciferase assay was used to verify the binding sites between MONC and miR-636 and between miR-636 and GLCE. Double fluorescence in situ hybridization was used to locate MONC and miR-636 in cells. ECSCs were obtained by flow cytometry sorting assay. Sphere formation assay, CCK-8 assay, transwell invasion assay, cell cycle analysis and apoptosis assay were used to detect the effects of MONC/miR-636/GLCE axis on the malignant biological behavior of ECSCs and ECCs. The effect of MONC on the epithelial-to-mesenchymal transition (EMT) process was detected using western blot. Finally, we conducted in vivo verification through Tumor xenografts in BALB/C nude mice.ResultsIn this study, we found MONC is low expression in endometrial carcinoma (EC) and patients in the MONC high-expression group had a better prognosis. MONC and miR-636 are relatively co-localized in the cytoplasm. MONC directly inhibits the malignant biological behavior of ECSCs and ECCs by directly inhibiting miR-636. Simultaneously, miR-636 may indirectly reduce the expression of MONC. Down-regulation of miR-636 may promote GLCE expression by targeting the 3'-untranslated region (UTR) of the downstream gene GLCE, thereby inhibiting the progression of ECSCs. MONC combined with miR-636 inhibited tumor epithelial-to-mesenchymal transition (EMT) process. In addition, we verified the tumor suppressive effect of MONC in nude mice, miR-636 can rescue the tumor suppressive effect of overexpressing MONC.ConclusionsIn conclusion, this study showed that MONC inhibits the malignant phenotypes of ECSCs and ECCs by regulating the miR-636/GLCE axis. Thus the MONC/miR-636/GLCE axis may provide novel treatment avenues for human EC.

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Silencing of Long Non-Coding RNA LINC01106 Suppresses the Proliferation, Migration and Invasion of Endometrial Cancer Cells Through Regulating the miR-449a/MET Axis

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