MicroRNA-135a acts as a putative tumor suppressor by directly targeting very low density lipoprotein receptor in human gallbladder cancer.

The precise functions and mechanisms of microRNAs (miR) in gallbladder cancer (GBC) remain elusive. In this study, we found that miR-135a-5p expression is often dampened and correlated with neoplasm histologic grade in GBC. MicroRNA-135a-5p introduction clearly inhibited GBC cell proliferation in vitro and in vivo. Moreover, very low density lipoprotein receptor (VLDLR), which is often upregulated in GBC tissues, was identified as a direct functional target of miR-135a-5p. Furthermore, the p38 MAPK pathway was proven to be involved in miR-135a-VLDLR downstream signaling. Together, these results suggested that the miR-135a-VLDLR-p38 axis may contribute to GBC cell proliferation.