Abstract: Objective To investigate the role of myosin heavy chain 9 (MYH9) in regulation of cell proliferation, apoptosis, and cisplatin sensitivity of non-small cell lung cancer (NSCLC). Methods Six NSCLC cell lines (A549, H1299, H1975, SPCA1, H322, and H460) and a normal bronchial epithelial cell line (16HBE) were examined for MYH9 expression using Western blotting. Immunohistochemical staining was used to detect MYH9 expression in a tissue microarray containing 49 NSCLC and 43 adjacent tissue specimens. MYH9 knockout cell models were established in H1299 and H1975 cells using CRISPR/Cas9 technology, and the changes in cell proliferation cell were assessed using cell counting kit-8 (CCK8) and clone formation assays; Western blotting and flow cytometry were used to detect apoptosis of the cell models, and cisplatin sensitivity of the cells was evaluated using IC50 assay. The growth of tumor xenografts derived from NSCLC with or without MYH9 knockout was observed in nude mice. Results MYH9 expression was significantly upregulated in NSCLC (P<0.001), and the patients with high MYH9 expression had a significantly shorter survival time (P=0.023). In cultured NSCLC cells, MYH9 knockout obviously inhibited cell proliferation (P<0.001), promoted cell apoptosis (P<0.05), and increased their chemosensitivity of cisplatin. In the tumor-bearing mouse models, the NSCLC cells with MYH9 knockout showed a significantly lower growth rate (P<0.05). Western blotting showed that MYH9 knockout inactivated the AKT/c-Myc axis (P<0.05) to inhibit the expression of BCL2-like protein 1 (P<0.05), promoted the expression of BH3-interacting domain death agonist and the apoptosis regulator BAX (P<0.05), and activated apoptosis-related proteins caspase-3 and caspase-9 (P<0.05). Conclusion High expression of MYH9 contributes to NSCLC progression by inhibiting cell apoptosis via activating the AKT/c-Myc axis.

Key words: MYH9; CRISPR-Cas9; non-small cell lung cancer; cell apoptosis; cisplatin resistance; Akt/c-Myc signaling