期刊
ONCOTARGETS AND THERAPY
卷 12, 期 -, 页码 7307-7321出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/OTT.S213371
关键词
papillary thyroid cancer; microRNA-675; mitogen-activated protein kinase 1; component of mitochondrial RNA processing endoribonuclease
Background: MicroRNA-675-5p (miR-675-5p) is dysregulated in multiple human cancers, but its involvement in papillary thyroid cancer (PTC) remains to be investigated. This study aimed to examine the expression pattern of miR-675 in PTC, determine the effects of miR-675 on regulating the progression of PTC, and to explore the underlying molecular mechanisms. Methods: The expression profile of miR-675 in PTC tissues and cell lines was determined using RT-qPCR. CCK-8, transwell migration and invasion assays, and xenograft tumors in nude mice were employed to analyze proliferation, in vitro migration and invasion, and in vivo tumor growth of PTC cells, respectively. The putative target of miR-675 was predicted using bioinformatic algorithms and was confirmed using luciferase reporter assays, RT-qPCR, and Western blotting. Results: miR-675 expression was decreased in PTC tissues and cell lines. A low level of miR-675 expression was significantly correlated with lymphatic metastasis and TNM stage in PTC patients. Ectopic miR-675 expression suppressed PTC cell proliferation, migration, and invasion in vitro and hindered tumor growth in vivo. Mitogen-activated protein kinase 1 (MAPK1) was found to be the direct target gene of miR-675 in PTC cells. MAPK1 reintroduction negated the tumor-suppressing effect of miR-675 overexpression in PTC cells. Furthermore, the lncRNA mitochondrial RNA processing endoribonuclease (RMRP) functioned as a ceRNA of miR-675 in PTC cells. Silencing RMRP expression inhibited the growth and metastasis of PTC cells by sponging miR-675 and regulating MAPK1. Conclusion: These findings revealed that miR-675 directly targets MAPK1 and is sponged by lncRNA RMRP to inhibit the oncogenicity of PTC, suggesting the RMRP-miR-675-MAPK1 pathway is an effective target for the treatment of PTC patients.
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