MyoD1 promotes the transcription of BIK and plays an apoptosis-promoting role in the development of gastric cancer

ABSTRACT

Myogenic differentiation (MyoD) 1, which is known as a pivotal transcription factor during myogenesis, has been proven dysregulated in several cancers. However, litter is known about the precise role and downstream genes of MyoD1 in gastric cancer (GC) cells. Here, we report that MyoD1 is lowly expressed in primary GC tissues and cells. In our experiments, overexpression of MyoD1 inhibited cell proliferation. Downstream genes of MyoD1 regulation were investigated using RNA-Seq. As a result, 138 up-regulated genes and 20 down-regulated genes and 27 up-regulated lncRNAs and 20 down-regulated lncRNAs were identified in MyoD1 overexpressed MKN-45 cells, which participated in epithelial cell signaling in Helicobacter pylori infection, glycosaminoglycan biosynthesis (keratan sulfate), notch signaling pathway, and others. Among these genes, BIK was directly regulated by MyoD1 in GC cells and inhibited cancer cell proliferation. The BIK knockdown rescued the effects of MyoD1 overexpression on GC cells. In conclusion, MyoD1 inhibited cell proliferation via 158 genes and 47 lncRNAs downstream directly or indirectly that participated in multiple signaling pathways in GC, and among these, MyoD1 promotes BIK transcription by binding to its promoter, then promotes BIK-Bcl2-caspase 3 axis and regulates GC cell apoptosis.

KEYWORDS:

• Myogenic differentiation 1
• gastric cancer
• Bcl-2-interacting killer
• proliferation
• apoptosis

Acknowledgements

The authors gratefully acknowledge the Institute of Genetics and Development Biology, Translational Medicine Institute, Xi’an Jiaotong University, Biomedical Experiment Center, Xian Jiaotong University, China.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Statement of ethics

The study was approved by the Ethical Committee of Xi’an Jiaotong University, and guidelines of the committee were followed. Informed consent was obtained from all patients before collection of samples.

Author contributions

Shuqun Zhang, Yannan Qin, Chen Huang conceived and designed the experiments. Fei Wu, Jinyuan Zhang, Qiuyu Jiang, Qian Li, Fang Li, Jia Li, and Wei Lv performed the experiments. Xiaofei Wang analyzed the data. Fei Wu, Yannan Qin, and Chen Huang wrote the paper.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

Supplemental material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15384101.2024.2348344

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (No. 82103212), Shaanxi Province natural science basic research program (2022JQ-842) and Construction project of Key Laboratory of Tumor Prevention and Treatment of Integrated Traditional Chinese and Western Medicine of Shaanxi Province (2022-ZXY-SYS-002).