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Title: METTL14 promotes tumorigenesis by regulating lncRNA OIP5-AS1/miR-98/ADAMTS8 signaling in papillary thyroid cancer. Author: Zhang X, Li D, Jia C, Cai H, Lv Z, Wu B. Journal: Cell Death Dis; 2021 Jun 15; 12(6):617. PubMed ID: 34131102. Abstract: BACKGROUND: Papillary thyroid cancer (PTC) is the most common type of cancer of the endocrine system. Long noncoding RNAs (lncRNAs) are emerging as a novel class of gene expression regulators associated with tumorigenesis. Through preexisting databases available for differentially expressed lncRNAs in PTC, we uncovered that lncRNA OIP5-AS1 was significantly upregulated in PTC tissues. However, the function and the underlying mechanism of OIP5-AS1 in PTC are poorly understood. METHODS: Expression of lncRNA OIP5-AS1 and miR-98 in PTC tissue and cells were measured by quantitative real-time PCR (qRT-PCR). And expression of METTL14 and ADAMTS8 in PTC tissue and cells were measured by qRT-PCR and western blot. The biological functions of METTL14, OIP5-AS1, and ADAMTS8 were examined using MTT, colony formation, transwell, and wound healing assays in PTC cells. The relationship between METTL14 and OIP5-AS1 were evaluated using RNA immunoprecipitation (RIP) and RNA pull down assay. And the relationship between miR-98 and ADAMTS8 were examined by luciferase reporter assay. For in vivo experiments, a xenograft model was used to investigate the effects of OIP5-AS1 and ADAMTS8 in PTC. RESULTS: Functional validation revealed that OIP5-AS1 overexpression promotes PTC cell proliferation, migration/invasion in vitro and in vivo, while OIP5-AS1 knockdown shows an opposite effect. Mechanistically, OIP5-AS1 acts as a target of miR-98, which activates ADAMTS8. OIP5-AS1 promotes PTC cell progression through miR-98/ADAMTS8 and EGFR, MEK/ERK pathways. Furthermore, RIP and RNA pull down assays identified OIP5-AS1 as the downstream target of METTL14. Overexpression of METTL14 suppresses PTC cell proliferation and migration/invasion through inhibiting OIP5-AS1 expression and regulating EGFR, MEK/ERK pathways. CONCLUSIONS: Collectively, our findings demonstrate that OIP5-AS1 is a METTL14-regulated lncRNA that plays an important role in PTC progression and offers new insights into the regulatory mechanisms underlying PTC development.[Abstract] [Full Text] [Related] [New Search]