TONSL在食管癌中的表达及其影响食管鳞癌细胞增殖的机制

doi:10.3969/j.issn.1004-616x.2023.06.002

Abstract

Abstract: OBJECTIVE：To investigate the expression of tonsoku-like DNA repair protein (TONSL) in esophageal carcinoma and its effect and mechanism on the proliferation of esophageal squamous cell carcinoma. METHODS：Databases such as cBioPortal，GEPIA and PRIDE were used to analyze changes in TONSL genome copy number and its transcription and translation levels in esophageal cancer. The expression of TONSL in esophageal squamous cell carcinoma and normal esophageal tissues was detected by immunohistochemistry. Small interfering RNA (siRNA) was used to construct a TONSL knockdown esophageal squamous cell model. The effect of TONSL knockdown on the proliferation of esophageal squamous cell carcinoma cells was studied by colony formation assay and EdU assay，while the changes of phosphorylated activation levels of ATM serine/threonine kinase (ATM) and checkpoint kinase 2 (CHK2)，two DNA damage repair related marker proteins in esophageal squamous cell carcinoma cells was detected by Western blot. RESULTS：Compared with normal esophageal tissue，copy number amplification of TONSL was common in esophageal cancer，and its mRNA and protein levels in esophageal cancer were up-regulated compared with those in normal esophageal tissues (P<0.05)，and high TONSL expression was associated with poor prognosis of patients with esophageal carcinoma (P<0.05). The results of immunohistochemistry also showed that TONSL was up-regulated in esophageal squamous cell carcinoma. The results of colony formation assay and EdU assay showed that knockdown of TONSL inhibited the proliferation of esophageal squamous cell carcinoma cells (P<0.05). Moreover，TONSL knockdown induced up-regulation of the phosphorylation of ATM serine/threonine kinase (ATM) and checkpoint kinase 2 (CHK2) in esophageal squamous cell carcinoma cells. CONCLUSION：TONSL was up-regulated in esophageal squamous cell carcinoma and promoted the proliferation of esophageal squamous cell carcinoma by participating in DNA damage repair.

Key words: esophageal squamous cell carcinomar, TONSL, cell proliferation, DNA damage repair

CLC Number:

R735.1

ZHENG Yaqi, ZHAO Ziting, PAN Deyuan, LIU Luxin, XU Xiue, LIAO Liandi, WANG Shaohong, LI Enmin, XU Liyan. The expression of tonsoku-like DNA repair protein in esophageal carcinoma and its effect on the proliferation of esophageal squamous cell carcinoma[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(6): 412-419.

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The expression of tonsoku-like DNA repair protein in esophageal carcinoma and its effect on the proliferation of esophageal squamous cell carcinoma

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