MiR-148a-3p acts as tumor suppressor and inhibits HCC cells malignancy by targeting ITGA5 through PI3K/Akt pathway. (A) Cell viability was evaluated in miR-148a or control transfected human HCC cells (LM3, PLC or 7721, respectively) using CCK-8 assay. Data represent the mean with s.d. (n=3). *P<0.05, **P<0.01, ****P<0.0001. (B) Invasion assays for indicated HCC cells were performed by transwell inserts with Matrigel. Scale Bar, 50μm. ***P<0.001, ****P<0.0001. (C) Representative images of wound healing assay of HCC cells transfected with miR-148a-3p as monitored 24 h after scratching. Wound-healing index was quantified. Data represent mean with s.d. (n=3). *P<0.05, **P<0.01. (D) Venn diagram showing the overlap of predicted target genes of miR-148a-3p in 5 miRNA target prediction databases (miRDB, picTar, ENCORI, TargetScan, miRTarBase). (E) The expression level of ITGA5 was significantly down-regulated in LM3 cells over-expressed miR-148a-3p. (F) Dual luciferase reporter assay in HEK293T cells co-transfected with firefly luciferase constructs containing the wild type or mutant miR-138a-3p site of ITGA5 3'UTR and firefly luciferase activity was normalized to Renilla luciferase (n=3). WT, wild type; Mu, mutant; **P<0.01. (G) miR-148a-3p impaired malignancy of HCC cells through inhibiting ITGA5/PI3K/Akt signaling.