MicroRNA-135a acts as a putative tumor suppressor by directly targeting very low density lipoprotein receptor in human gallbladder cancer.
Bottom Line: 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.
Affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.Show MeSH
Related in: MedlinePlus
Mentions: Potential targets of miR-135a-5p were predicted by TargetScan (http://www.targetscan.org) and PicTar (http://pictar.mdc-berlin.de), and mRNA microarray assays were carried out in EH-GB1 cells transfected with miR-135a-5p mimic. Six genes were considered as the candidate target gene (Fig. 3a). In GBC-SD cells, miR-135a-5p mimic could dampen the mRNA levels of SP3 and VLDLR, which have inhibitory effects on cancer cell proliferation (Fig. 3b).(11,12) Very low density lipoprotein receptor siRNAs could clearly inhibit the proliferation of both EH-GB1 and GBC-SD cells, yet SP3 siRNAs did not affect GBC-SD cell proliferation (Fig. S4), indicating that VLDLR was responsible for the effect of miR-135a-5p on GBC cell proliferation.
Affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.