Abstract
BackgroundPapillary 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.MethodsExpression 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.ResultsFunctional 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.ConclusionsCollectively, 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.
Highlights
The incidence of thyroid cancer is constantly rising in the recent years, becoming the most common form of endocrine malignancy [1,2,3]
Increasing evidences suggest that alterations in the expression of m6A methylation regulators, especially methyltransferase-like 14 (METTL14), can suppress cell proliferation and metastasis of cancers regulated by Long noncoding RNAs (lncRNAs) and mRNAs, such as XIST, SOX4, and PERP [8,9,10]
OIP5-AS1 and ADAMTS8 are upregulated in Papillary thyroid cancer (PTC) tissues To identify lncRNAs involved in PTC, we analyzed total
Summary
The incidence of thyroid cancer is constantly rising in the recent years, becoming the most common form of endocrine malignancy [1,2,3]. N6-methyladenosine (m6A) methylation plays a vital role in maintaining the functions and characteristics of tumor cells during tumorigenesis and development. Many studies have reported that long non-coding RNAs (lncRNAs) harboring m6A modification have significant effects on target genes via protein-RNA interaction in a variety of tumors including cervical, breast, colorectal, and thyroid cancers [5, 6]. Increasing evidences suggest that alterations in the expression of m6A methylation regulators, especially METTL14, can suppress cell proliferation and metastasis of cancers regulated by lncRNAs and mRNAs, such as XIST, SOX4, and PERP [8,9,10]. 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. The function and the underlying mechanism of OIP5-AS1 in PTC are poorly understood
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