Journal
JOURNAL OF TRANSLATIONAL MEDICINE
Volume 20, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12967-022-03818-5
Keywords
Esophageal squamous cell carcinoma; Radioresistance; WGCNA; miR-4443; PTPRJ axis; Apoptosis
Categories
Funding
- National Natural Science Foundation of China
- Shaan Xi Province key research and development program [81872471]
- Talent Foundation from the Second Affiliated Hospital of Xi'an Jiaotong University [2021SF-122, 2022SF-092]
- [RC(SM)201904]
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In this study, miR-4443 was found to promote radiotherapy resistance in ESCC cells by regulating PTPRJ expression, providing a new perspective and clue to alleviate radioresistance.
Background: Radiotherapy is one of the main treatments for esophageal squamous cell carcinoma (ESCC), but its efficacy is limited by radioresistance. MicroRNAs play a crucial role in posttranscriptional regulation, which is linked to the cancer response to radiation. Methods: We successfully established a radioresistant cell line model by using fractionated irradiation. qRT-PCR was adopted to detect the expression of miR-4443 in human normal esophageal cell lines, tumor cells, and radioresistant cells. Next, CCK-8, colony formation, apoptosis, and cell cycle assays were used to assess the biological effect of miR-4443. Weighted gene coexpression network analysis (WGCNA) was performed to identify potential radiosensitivity-related genes. Additionally, we predicted the probable targets of the miRNA using bioinformatic methods and confirmed them using Western blot. Results: miR-4443 was significantly upregulated in radioresistant ESCC cells. Enhancement of miR-4443 further decreased the radiosensitivity of ESCC cells, while inhibition of miR-4443 increased the radiosensitivity of ESCC cells. Notably, miR-4443 modulated radiosensitivity by influencing DNA damage repair, apoptosis, and G2 cycle arrest. By using WGCNA and experimental validation, we identified PTPRJ as a key target for miRNA-4443 to regulate radiosensitivity. The effects of miR-4443 overexpression or inhibition could be reversed by increasing or decreasing PTPRJ expression. Conclusion: In this study, miR-4443 is found to promote radiotherapy resistance in ESCC cells by regulating PTPRJ expression, which provides a new perspective and clue to alleviate radioresistance.
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