Klf4 inhibits tumor growth and metastasis by targeting microRNA-31 in human hepatocellular carcinoma.

MicroRNAs (miRNAs or miRs) are short, endogenous non-coding RNA molecules, demonstrating abnormal expression in cancer initiation and progression. In this study, we profiled 18 differentially regulated miRNAs, including miRNA‑31, using miRNA array. Kruppel (or Krüppel)-like factor 4 (Klf4) is a transcription factor and putative tumor suppressor. Both were found to be significantly downregulated in liver cancer tissues and cells. However, little is known about the correlation between Klf4 and miRNA‑31 in hepatocellular carcinoma (HCC). The mRNA expression of Klf4 was decreased and inversely associated with the clinical stage, T classification and hepatitis B in patients with HCC, while the expression of miR‑31 was lower (r=0.326, P=0.018). Using cell counting kit 8 (CCK8) and Transwell migration assays, we found that Klf4 and miR‑31 inhibited the proliferation and metastasis of liver cancer cells. Moreover, we demonstrated that Klf4 directly binds to the promoter of miR‑31 and activates its transcription. In vitro experiments confirmed that Klf4 regulated miR‑31 and thereby inhibited HCC cell growth and metastasis. Taken together, our findings indicate that Klf4 directly regulates miR‑31 in HCC. Thus, miR-31 may serve as a potential diagnostic marker and therapeutic target in HCC.