Long Non-Coding RNA MAPK8IP1P2 Inhibits Lymphatic Metastasis of Thyroid Cancer by Activating Hippo Signaling via Sponging miR-146b-3p

Frontiers in Oncology

Gianlorenzo Dionigi¹  Nan Liang²  Changlin Li²  Qingfeng Fu²  Jiao Zhang²  Xiaoli Liu²  Jingwei Xin²  Yantao Fu²  Xuehai Bian²  Hui Sun²  Shijie Li²  Yishen Zhao²  Li Fang² 

[1] Division for Endocrine and Minimally Invasive Surgery, Department of Human Pathology in Adulthood and Childhood “G. Barresi”, University Hospital “G. Martino”, University of Messina, Messina, Italy;Division of Thyroid Surgery, China–Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Changchun, China;

关键词: thyroid cancer;    lymph node metastasis;    anoikis resistance;    MAPK8IP1P2;    Hippo signaling;   

DOI  :  10.3389/fonc.2020.600927

来源: DOAJ

【 摘 要 】

The principal issue derived from thyroid cancer is its high propensity to metastasize to the lymph node. Aberrant exprssion of long non-coding RNAs have been extensively reported to be significantly correlated with lymphatic metastasis of thyroid cancer. However, the clinical significance and functional role of lncRNA-MAPK8IP1P2 in lymphatic metastasis of thyroid cancer remain unclear. Here, we reported that MAPK8IP1P2 was downregulated in thyroid cancer tissues with lymphatic metastasis. Upregulating MAPK8IP1P2 inhibited, while silencing MAPK8IP1P2 enhanced anoikis resistance in vitro and lymphatic metastasis of thyroid cancer cells in vivo. Mechanistically, MAPK8IP1P2 activated Hippo signaling by sponging miR-146b-3p to disrupt the inhibitory effect of miR-146b-3p on NF2, RASSF1, and RASSF5 expression, which further inhibited anoikis resistance and lymphatic metastasis in thyroid cancer. Importantly, miR-146b-3p mimics reversed the inhibitory effect of MAPK8IP1P2 overexpression on anoikis resistance of thyroid cancer cells. In conclusion, our findings suggest that MAPK8IP1P2 may serve as a potential biomarker to predict lymphatic metastasis in thyroid cancer, or a potential therapeutic target in lymphatic metastatic thyroid cancer.

【 授权许可】

Unknown