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Long Non-coding Antisense RNA TNRC6C-AS1 Is Activated in Papillary Thyroid Cancer and Promotes Cancer Progression by Suppressing TNRC6C Expression.

ABSTRACT: Context: Evidences have shown the important role of long non-coding antisense RNAs in regulating its cognate sense gene in cancer biology. Objective: Investigate the regulatory role of a long non-coding antisense RNA TNRC6C-AS1 on its sense partner TNRC6C, and their effects on the aggressiveness and iodine-uptake ability of papillary thyroid cancer (PTC). Design: TNRC6C-AS1 was identified as the target long non-coding RNA in PTC by using microarray analysis and computational analysis. In vitro gain/loss-of-function experiments were performed to investigate the effects of TNRC6C-AS1 and TNRC6C on proliferation, apoptosis, migration, invasion and iodine-uptake ability of TPC1 cells. Expression levels of TNRC6C-AS1 and TNRC6C of 30 cases of PTC tissues and its adjacent normal thyroid tissues were determined. Results: Downregulation of TNRC6C-AS1 or overexpression of TNRC6C inhibited proliferation, migration and invasion of TPC1 cells, while apoptosis and iodine uptake was promoted in TPC1 cells. Suppression of TNRC6C-AS1 significantly increased the expression of TNRC6C in TPC1 cells. The inhibitory effect of TNRC6C-AS1 knockdown on cell proliferation, migration and invasion was attenuated when the expression of TNRC6C was suppressed simultaneously, indicating TNRC6C is a functional target of TNRC6C-AS1. The expression of TNRC6C-AS1 was significantly higher, while the TNRC6C mRNA and protein were significantly lower in PTC tissues than normal adjacent tissues. There was a significant inverse correlation between TNRC6C-AS1 and TNRC6C mRNA in PTC tissue samples. Conclusions: TNRC6C-AS1 promotes the progression of PTC and inhibits its ability of iodine accumulation by suppressing the expression of TNRC6C. Targeting TNRC6C-AS1 - TNRC6C axis may be a new promising treatment for PTC.

SUBMITTER: Muhanhali D

PROVIDER: S-EPMC6046411 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Long Non-coding Antisense RNA TNRC6C-AS1 Is Activated in Papillary Thyroid Cancer and Promotes Cancer Progression by Suppressing TNRC6C Expression.

Muhanhali Dilidaer D Zhai Tianyu T Jiang Jingjing J Ai Zhilong Z Zhu Wei W Ling Yan Y

Frontiers in endocrinology 20180709

Context: Evidences have shown the important role of long non-coding antisense RNAs in regulating its cognate sense gene in cancer biology. Objective: Investigate the regulatory role of a long non-coding antisense RNA TNRC6C-AS1 on its sense partner TNRC6C, and their effects on the aggressiveness and iodine-uptake ability of papillary thyroid cancer (PTC). Design: TNRC6C-AS1 was identified as the target long non-coding RNA in PTC by using microarray analysis and computational ...[more]

PMID: 30038597

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Project description: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.

Dataset Information

Long Non-coding Antisense RNA TNRC6C-AS1 Is Activated in Papillary Thyroid Cancer and Promotes Cancer Progression by Suppressing TNRC6C Expression.

Publications

Long Non-coding Antisense RNA TNRC6C-AS1 Is Activated in Papillary Thyroid Cancer and Promotes Cancer Progression by Suppressing TNRC6C Expression.

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