Effects of miR 192 5p on stem cell like phenotype of pancreatic cancer cells via ATXN7

Abstract

Pancreatic cancer is one of the
deadliest cancers in the world. Cancer stem cells (CSC) play a critical role
in the genesis, progression, metastasis, chemical resistance and recurrence of tumors. Cumulative studies
have shown that miR 192 5p regulates the stem cell like phenotype in mal ignancies. However, the
mechanism of the effect of miR 192 5p on the stem cell like phenotype of pancreatic cancer remains to be
studied. In this study, we predicted through star B ase database that the expression of miR 192 5p was
abnormally high in tissues . After the stem cell like cells of SW1990 cells enriched in Serum free Medium
(SFM), RT qPCR revealed significantly high expression of miR 192 5p in these cells. In addition, the effects
of miR 192 5p on SW1990 cell proliferation and stem cell like proper ties were examined by CCK 8, EdU
staining, clone formation and sphere formation assay, respectively. The results showed that overexpression
or knockdown of miR 192 5p significantly upregulated or decreased the proliferation activity, EdU positive
cell prop ortion, number of clones and number of spheres in SW1990 cells. We further predicted the
downstream target of miR 192 5p by PITA, RNA22 and miRmap, and verified it by dual luciferase reporter
gene assay and Western blotting. The results showed that ATXN7 w as the downstream target of miR 192
5p, and miR 192 5p negatively regulated the expression of ATXN7. The database predicted that ATXN7
expression was significantly lower in pancreatic cancer tissues and negatively correlated with miR 192 5p
expression. The results of functional experiments showed that the overexpressing ATXN7 decreased the
proliferation activity, EdU positive cell percentage, number of clones and number of spheres of SW1990
cells. However, simultaneous overexpressing miR 192 5p and ATXN7 re scued these phenotypes of
SW1990 cells. In conclusion, the present study found that miR 192 5p was abnormal and highly expressed
in pancreatic cancer, and miR 192 5p promoted pancreatic cancer cell proliferation and stem cell like
phenotype by inhibiting t he expression of ATXN7.