High expression of MYH9 inhibits apoptosis of non-small cell lung cancer cells through activating the AKT/c-Myc pathway.
10.12122/j.issn.1673-4254.2023.04.04
- Author:
Fang LIU
1
;
Lanzhu PENG
2
;
Jingle XI
1
Author Information
1. Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
2. Cancer Center, Integrated Hospital of Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou 510315, China.
- Publication Type:Journal Article
- Keywords:
Akt/c-Myc signaling;
CRISPR-Cas9;
MYH9;
cell apoptosis;
cisplatin resistance;
non-small cell lung cancer
- MeSH:
Animals;
Humans;
Mice;
Apoptosis;
Carcinoma, Non-Small-Cell Lung/metabolism*;
Cell Line, Tumor;
Cell Proliferation;
Cisplatin/pharmacology*;
Cytoskeletal Proteins/metabolism*;
Lung Neoplasms/metabolism*;
Mice, Nude;
Myosin Heavy Chains/metabolism*;
Proto-Oncogene Proteins c-akt/metabolism*;
Signal Transduction
- From:
Journal of Southern Medical University
2023;43(4):527-536
- CountryChina
- Language:Chinese
-
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.
