MiR-199a-3p promotes gastric cancer progression by targeting ZHX1

• MicroRNAs (miRNAs) have emerged as critical epigenetic regulators involved in cancer progression.
• To our knowledge, this is the first regular article to demonstrate the association between miR-199a-3p and gastric cancer.
• Here we presented that he miR-199a-3p act as an oncogenic role in inducing gastric cell growth and inhibiting gastric cell apoptosis.
• For the first time, the fact that zinc fingers and homeoboxes 1(ZHX1) was directly regulated by miR-199a-3p was reported.
• ZHX1 was rarely studied in cancer area, let alone in the gastric cancer. We showed its suppressive function in regulating gastric cancer cell growth.

Accumulating evidence has indicated that microRNAs (miRNAs) act as critical epigenetic regulators in tumor carcinogenesis. Here, we report that miR-199a-3p was significantly upregulated in gastric cancer (GC) cell lines and tissues. Functional studies demonstrated that miR-199a-3p dramatically increased cell proliferation and suppressed cell apoptosis both in vitro and in vivo. Furthermore, the transcriptional regulator zinc fingers and homeoboxes 1 (ZHX1) was identified as one of the direct downstream targets of miR-199a-3p, miR-199a-3p bound to the ZHX1 3′ untranslated region (3′UTR) to regulate ZHX1 protein expression. In addition, the expression of miR-199a-3p was inversely associated with that of ZHX1 in GC cell lines. Overexpression of miR-199a-3p in SGC-7901 cells inhibited ZHX1 expression, while reduction in miR-199a-3p by inhibitors in NCI-N87 cells enhanced ZHX1 expression. Moreover, restoring ZHX1 expression in SGC-7901/miR-199a-3p cells inhibited the cell proliferation induced by miR-199a-3p. Taken together, these findings suggest that miR-199a-3p may function as a novel tumor promoter in GC and its oncogenic activity may involve the direct targeting and inhibition of ZHX1.