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
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Mentions: MicrRNA-135a-5p mimic transfection could inhibit the proliferation and colony formation ability of GBC-SD and EH-GB1 cells (Fig. S2b,c), and arrest the cells in G1/S phase (Fig. S3a). Caspase-Glo 3/7 Assay (Promega) showed that miR-135a-5p could slightly upregulate caspase 3/7 activity (Fig. S3b), whereas SA-β-gal staining showed that miR-135a-5p had no obvious influence on GBC cellular senescence (Fig. S3c). We then established stable GBC-SD and EH-GB1 cells overexpressing miR-135a via lentivirus (Fig. S2d), and found that the proliferation rates of lenti-miR-135a GBC cells were significantly decreased compared with those cells infected with lenti-GFP (Fig. 2a,b). The cells stably expressing miR-135a or GFP were s.c. injected into nude mice. After 6 weeks, the mice were killed and the xenografts were evaluated. The tumors derived from the miR-135a cells were much smaller than those from the GFP cells (Fig. 2c). In sum, miR-135a-5p could inhibit the proliferation of GBC cells both in vitro and in vivo.
Affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.