The ATPase subunit of ATP6V1C1 inhibits autophagy and enhances radiotherapy resistance in esophageal squamous cell carcinoma.

Abstract

Radiotherapy is one of the primary therapeutic modalities for patients diagnosed esophageal squamous cell carcinoma(ESCC). Previous studies have shown that chemotherapy resistance could be linked with the overexpression vascular ATPases(V-ATPase) subunits genes. However, it is unknown whether V-ATPase subunits genes play a role in radiotherapy resistance. The aim of this study was to investigate the effect of the ATP6V1C1 in radiotherapy resistance. siRNA and plasmids were used to transfect low expression of ATP6V1C1 in TE13 (human ESCC cell) and high expressed in ECA109 (human ESCC cell), respectively. To observe proliferation, radiosensitivity, apoptosis and DNA-damage response, colony formation assays, EDU assays, flow cytometry and γH2AX assay were used with or without radiation exposure, separately. The quantities of the autophagosomes and autolysosomes by immunofluorescence were calculated. Autophagic microstructure were discovered by transmission electron microscopy, and the study also repeated in vivo by nude mice. Western blot assay was applied to prove changes in relative proteins. We found that suppressing ATP6V1C1 increased the sensitivity of ESCC cells after RT. Silencing ATP6V1C1 with IR suppressed the tumor growth and promoted autophagy. Besides, the underlying mechanism of ATP6V1C1, which is not fatally disrupted, is that ATP6V1C1 with ionizing radiation (IR)decreased apoptosis and inhibited autophagy may by activating mTOR signaling to suppress radiosensitivity for ESCC cells. Thus, we first reported that the ATP6V1C1 may represent a potential radiotherapeutic target by effect on radiation sensitivity for ESCC.

• Authors: Xijuan Yao, Hui Chen, Bing Xu, Jing Lu, Junjie Gu, Fangyu Chen, Mengyang Ju, Xinchen Sun
• Journal: Gene (Gene) Vol. 768 Pg. 145261 (Feb 05 2021) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 33183740 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• ATP6V1C1 protein, human
• Vacuolar Proton-Translocating ATPases

Topics

• Animals
• Apoptosis (genetics)
• Autophagy (genetics, physiology)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• DNA Repair (genetics)
• Esophageal Neoplasms (genetics, radiotherapy)
• Esophageal Squamous Cell Carcinoma (genetics, radiotherapy)
• Female
• Gene Silencing
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Radiation Tolerance (genetics)
• Radiation, Ionizing
• Vacuolar Proton-Translocating ATPases (genetics)
• Xenograft Model Antitumor Assays