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

Chien An Chu, Chung Ta Lee, Jenq Chang Lee, Yi Wen Wang, Ching Tang Huang, Sheng Hui Lan, Peng Chan Lin, Bo Wen Lin, Yu Feng Tian, Hsiao Sheng Liu, Nan Haw Chow

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

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. Fund: NCKU Hospital, Taiwan, Ministry of Science and Technology, Taiwan.

Original languageEnglish
Pages (from-to)270-281
Number of pages12
JournalEBioMedicine
Volume43
DOIs
Publication statusPublished - 2019 May

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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