lncRNA HAND2‐AS1 overexpression inhibits cancer cell proliferation in hepatocellular carcinoma by downregulating RUNX2 expression

Background The long non‐coding RNA HAND2 antisense RNA 1 (HAND2‐AS1) acts as a tumor suppressor in several malignancies, but its role in hepatocellular carcinoma (HCC) remains unknown. In this study, we aimed to investigate the function of HAND2‐AS1 in HCC. Methods The expression levels of HAND2‐AS1 and runt‐related transcription factor 2 (RUNX2) were determined in patients with HCC and HCC cell lines using quantitative real‐time polymerase chain reaction and western blot analyses. Cell proliferation was determined using Cell Counting Kit‐8 assay, and the correlation between HAND2‐AS1 and RUNX2 expression was also investigated. Results The plasma level of HAND2‐AS1 was downregulated and that of RUNX2 was upregulated in patients with early‐stage HCC compared with those in healthy controls. No significant differences in the plasma levels of HAND2‐AS1 and RUNX2 were found among hepatitis B virus (HBV)‐positive, hepatitis C virus (HCV)‐positive, and HBV‐ and HCV‐negative patients with HCC. The plasma levels of HAND2‐AS1 and RUNX2 were inversely correlated in the patient groups but not in the control group. HAND2‐AS1 overexpression led to the downregulation of RUNX2 expression in human HCC cells, whereas RUNX2 failed to significantly affect HAND2‐AS1 expression. HAND2‐AS1 overexpression inhibited and RUNX2 overexpression promoted the proliferation of HCC cells. RUNX2 overexpression attenuated the inhibitory effects of HAND2‐AS1 overexpression on cancer cell proliferation. Conclusion HAND2‐AS1 overexpression inhibits cancer cell proliferation in HCC by downregulating RUNX2 expression. HAND2‐AS1 overexpression significantly inhibited whereas RUNX2 overexpression significantly promoted the proliferation of SNU‐398 (A) and SNU‐182 (B) cells. RUNX2 overexpression partially compensated the adverse effects of HAND2‐AS1 overexpression on cancer cell proliferation. Consistent with the cell proliferation data, co‐transfection of HAND2‐AS1 and RUNX2 led to upregulation of HAND2‐AS1 and downregulation of HAND2‐AS1 mRNA expression (*p < 0.05).