The LncRNA H19/microRNA‐29b‐3p/HMGB1 signaling axis contributes to the regulation of lung cancer cell growth

The long non-coding RNA (lncRNA) H19 acts as a competitive endogenous RNA (ceRNA) of miR-29b-3p and has been reported to exert pro-tumorigenic roles in several cancer types. However, the role of lncRNA H19 in lung cancer is not fully understood. Here, we investigated the role of the lncRNA H19/microRNA-29b-3p (miR-29b-3p)/high mobility group box 1 (HMGB1) signaling pathway in lung cancer cell growth using 293T, NCI-H1975, Calu-3 and 2BS cell lines. Cell viability was determined using a cell counting kit-8 (CCK-8) assay, while apoptosis and cell cycle distribution were assessed by flow cytometry. Cell migration was detected using a wound healing assay. Cell invasion was evaluated by transwell assay. The expression of lncRNA H19, miR-29b-3p, HMGB1, toll-like receptor 4 (TLR4), and matrix metallopeptidase 9 (MMP-9) was measured by fluorescence quantitative PCR or western blotting. We demonstrated that miR-29b-3p could directly bind to both lncRNA H19 and HMGB1 by dual-luciferase reporter assay. Three shRNAs targeting lncRNA H19 (shlncRNA H19) were designed, and shlncRNA H19-2 was selected to investigate the function of lncRNA H19 in tumor cell biology. Compared with controls, lung cancer cells expressing shlncRNA H19 exhibited decreased proliferation, cell-cycle arrest at the G1 phase, increased levels of cell apoptosis, and reduced migration and invasion. Moreover, shlncRNA H19 upregulated the expression of miR-29b-3p and reduced the protein expression of HMGB1, TLR4, and MMP-9 in lung cancer cells. Together, our data indicate that the lncRNA H19/miRNA-29b-3p/HMGB1 signaling axis is involved in the regulation of lung cancer cell growth.