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.

Kindlin‑2 suppresses cervical cancer cell migration through AKT/mTOR‑mediated autophagy induction

“…This indicated that kindlin-2 inhibited cell migration by inducing autophagy. Similar results have been reported in other types of tumors, including hepatocellular carcinoma, renal cell cancer, and colorectal cancer (36)(37)(38). The present results also provide new evidence for the role of autophagy in the migration of cervical cancer cells.…”

MicroRNAs play an essential role in autophagy regulation in various disease phenotypes

“…AlkB homolog 5 (ALKBH5) is an N6‐methyladenosine (m6A) eraser protein. And, it inhibited autophagy of epithelial ovarian cancer through miR‐7 and regulated ovarian cancer proliferation and invasion via B cell lymphoma 2 (Bcl‐2) . MiR‐338‐5p promotes metastasis of colorectal cancer by inhibition of phosphatidylinositol 3‐kinase, catalytic subunit type 3‐mediated autophagy pathway .…”

“…And, it inhibited autophagy of epithelial ovarian cancer through miR-7 and regulated ovarian cancer proliferation and invasion via B cell lymphoma 2 (Bcl-2). 98 MiR-338-5p promotes metastasis of colorectal cancer by inhibition of phosphatidylinositol 3-kinase, catalytic subunit type 3-mediated autophagy pathway. 99 Pancreas ductal adenocarcinoma (PDAC) is one of the most common gastrointestinal malignancies.…”

The Roles of ceRNAs-Mediated Autophagy in Cancer Chemoresistance and Metastasis

“…The roles of ncRNAs such as lncRNAs [ 133 , 134 ], circRNAs [ 73 , 135 ], and miRNAs [ 133 , 136 ] have been recognized in cancer metastasis and autophagy. Figure 3 summarizes the potential roles of ceRNA-mediated autophagy in modulating metastasis.…”