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, Po-Wen Lin, Yu Feng Tian, Hsiao-Sheng Liu, Nan-Haw Chow

Research output: Contribution to journalArticle

2 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 1

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Class III Phosphatidylinositol 3-Kinases
Autophagy
Tumors
Colorectal Neoplasms
Genes
Neoplasm Metastasis
Biomarkers
Heterografts
Liver
Screening
Taiwan
Survival
Neoplasm Staging
Polyps
Experiments
Neoplasms
Spleen

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

@article{3d017e42474e40f08583e61e3d2cf3ca,
title = "MiR-338-5p promotes metastasis of colorectal cancer by inhibition of phosphatidylinositol 3-kinase, catalytic subunit type 3-mediated autophagy pathway",
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.",
author = "Chu, {Chien An} and Chung-Ta Lee and Jenq-Chang Lee and Wang, {Yi Wen} and Huang, {Ching Tang} and Lan, {Sheng Hui} and Peng-Chan Lin and Po-Wen Lin and Tian, {Yu Feng} and Hsiao-Sheng Liu and Nan-Haw Chow",
year = "2019",
month = "5",
day = "1",
doi = "10.1016/j.ebiom.2019.04.010",
language = "English",
volume = "43",
pages = "270--281",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier BV",

}

MiR-338-5p promotes metastasis of colorectal cancer by inhibition of phosphatidylinositol 3-kinase, catalytic subunit type 3-mediated autophagy pathway. / Chu, Chien An; Lee, Chung-Ta; Lee, Jenq-Chang; Wang, Yi Wen; Huang, Ching Tang; Lan, Sheng Hui; Lin, Peng-Chan; Lin, Po-Wen; Tian, Yu Feng; Liu, Hsiao-Sheng; Chow, Nan-Haw.

In: EBioMedicine, Vol. 43, 01.05.2019, p. 270-281.

Research output: Contribution to journalArticle

TY - JOUR

T1 - MiR-338-5p promotes metastasis of colorectal cancer by inhibition of phosphatidylinositol 3-kinase, catalytic subunit type 3-mediated autophagy pathway

AU - Chu, Chien An

AU - Lee, Chung-Ta

AU - Lee, Jenq-Chang

AU - Wang, Yi Wen

AU - Huang, Ching Tang

AU - Lan, Sheng Hui

AU - Lin, Peng-Chan

AU - Lin, Po-Wen

AU - Tian, Yu Feng

AU - Liu, Hsiao-Sheng

AU - Chow, Nan-Haw

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

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