MiR-338-5p promotes metastasis of colorectal cancer by inhibition of phosphatidylinositol 3-kinase, catalytic subunit type 3-mediated autophagy pathway

doi:10.1016/j.ebiom.2019.04.010

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Title:	MiR-338-5p promotes metastasis of colorectal cancer by inhibition of phosphatidylinositol 3-kinase, catalytic subunit type 3-mediated autophagy pathway
Authors:	Chu, Chien-An Lee, Chung-Ta Lee, Jenq-Chang Wang, Yi-Wen Huang, Ching-Tang Lan, Sheng-Hui Lin, Peng-Chan Lin, Bo-Wen Yu-Feng Tian(田宇峯) Liu, Hsiao-Sheng Chow, Nan-Haw
Contributors:	Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci Natl Cheng Kung Univ Hosp, Dept Pathol Natl Cheng Kung Univ, Coll Med Natl Cheng Kung Univ Hosp, Dept Pathol, Dou Liou Branch Natl Cheng Kung Univ Hosp, Coll Med, Dept Surg Natl Yang Ming Univ, Dept Life Sci Natl Yang Ming Univ, Inst Genome Sci Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol Natl Cheng Kung Univ, Coll Med, Dept Internal Med Chia Nan Univ Pharm & Sci, Dept Hlth & Nutr Chi Mei Med Ctr, Dept Surg, Div Colorectal Surg
Keywords:	miR-338-5p PIK3C3 Autophagy and colorectal cancer
Date:	2019-05
Issue Date:	2020-07-29 13:52:17 (UTC+8)
Publisher:	ELSEVIER SCIENCE BV
Abstract:	Background: In our preliminary screening, expression of miR-338-5p was found to be higher in primary colorectal cancer (CRC) with metastasis. The autophagy related gene- phosphatidylinositol 3-kinase, catalytic subunit type 3 (PIK3C3) appeared to be targeted by miR-338-5p. Here, we provide solid evidence in support of PIK3C3 involved in miR-338-5p related metastasis of CRC in vitro and in vivo. Methods: The potential clinical relevance of miR-338-5p and its target gene was analysed on benign colorectal polyps and primary CRCs by QPCR Mouse spleen xenograft experiment was performed to examine the importance of miR-338-5p for metastasis. Findings: PIK3C3 was one of target genes of miR-338-5p. In primary CRCs, expression of miR-338-5p is positively related to tumour staging, distant metastasis and poor patient survival. Patients with higher ratios of miR-338-5p/PIK3C3 also had significantly poor overall survival, supporting their significance in the progression of CRC. Over-expression of miR-338-5p promotes CRC metastasis to the liver and lung in vivo, in which PIK3C3 was down-regulated in the metastatic tumours. In contrast, overexpression of PIK3C3 in miR-338-5p stable cells inhibited the growth of metastatic tumours. Both migration and invasion of CRC in vitro induced by miR-338-5p are mediated by suppression of PIK3C3. Using forward and reverse approaches, autophagy was proved to involve in CRC migration and invasion induced by miR-338-5p. Interpretation: MiR-338-5p induces migration, invasion and metastasis of CRC in part through PIK3C3-related autophagy pathway. The miR-338-5p/PIK3C3 ratio may become a prognostic biomarker for CRC patients. (C) 2019 Published by Elsevier B.V.
Relation:	Ebiomedicine, v.43, pp.270-281
Appears in Collections:	[Dept. of Health and Nutrition (including master's program)] Periodical Articles

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