MiR-363-3p suppresses tumor growth and metastasis of colorectal cancer via targeting SphK2.

Aberrant expression of miR-363-3p is seen in a wide array of cancers. The exact function of miR-363-3p in colorectal cancer (CRC), and the underlying mechanisms remain undefined. In the current study, we observed a down-regulation of miR-363-3p in CRC tissues, along with a strong correlation between low miR-363-3p levels and clinico-pathological parameters like tumor stage and lymph node metastasis. Ectopic overexpression of miR-363-3p in HT29 and HCT116 cell lines effectively inhibited cell proliferation and metastasis, and promoted apoptosis. Concurrently, miR-363-3p inhibition facilitated cell proliferation and suppressed apoptosis. Consistent with the in vitro findings, tumor growth and metastasis were also suppressed by the overexpression of miR-363-3p in vivo. Furthermore, miR-363-3p overexpression resulted in a significant decrease in SphK2 mRNA and protein levels, while miR-363-3p inhibition elevated SphK2 levels in CRC cell lines. Overexpression of SphK2 significantly abrogated the effects of miR-363-3p on cell growth, apoptosis, and metastasis. Taken together, our findings establish miR-363-3p as a potential tumor suppressor in CRC with SphK2 as its downstream target.