FOSL1 transcriptionally regulates PHLDA2 to promote 5-FU resistance in colon cancer cells

作者全名："Liu, Guangyi; Wang, Huan; Ran, Rui; Wang, Yicheng; Li, Yang"

作者地址："[Liu, Guangyi; Ran, Rui; Wang, Yicheng; Li, Yang] Chongqing Med Univ, Affiliated Hosp 2, Dept Gastrointestinal Surg, Chongqing, Peoples R China; [Wang, Huan] Chongqing Med Univ, Affiliated Hosp 2, Dept Hlth Management Ctr, Chongqing, Peoples R China; [Li, Yang] Chongqing Med Univ, Affiliated Hosp 2, Dept Gastrointestinal Surg, 74 Linjiang Rd, Chongqing 400010, Peoples R China"

通信作者："Li, Y (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Gastrointestinal Surg, 74 Linjiang Rd, Chongqing 400010, Peoples R China."

来源：PATHOLOGY RESEARCH AND PRACTICE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001041517700001

JCR分区：Q2

影响因子：2.9

年份：2023

卷号：246

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：FOSL1; Colon cancer; PHLDA2; Chemotherapy resistance; 5-FU

摘要："Background: Tumor drug resistance is a leading cause of tumor treatment failure. To date, the association between FOS-Like antigen-1 (FOSL1) and chemotherapy sensitivity in colon cancer is unclear. The present study investigated the molecular mechanism of FOSL1 regulating 5-Fluorouracil (5-FU) resistance in colon cancer. Methods: FOSL1 expression in colon cancer was analyzed by bioinformatics methods, and its downstream regulatory factors were predicted. Pearson correlation analyzed the expression of FOSL1 and downstream regulatory gene. Meanwhile, the expression of FOSL1 and its downstream factor Pleckstrin Homology-Like Domain Family A Member 2 (PHLDA2) in colon cancer cell lines was measured by qRT-PCR and western blot. The regulatory relationship between FOSL1 and PHLDA2 was verified by chromatin immunoprecipitation (ChIP) assay and dualluciferase reporter assay. The effects of the FOSL1/PHLDA2 axis on the resistance in colon cancer cells to 5-FU were analyzed by cell experiments. Results: FOSL1 expression was evidently up-regulated in colon cancer and 5-FU resistant cells. FOSL1 was positively correlated with PHLDA2 in colon cancer. In vitro cell assays showed that low expression of FOSL1 significantly enhanced 5-FU sensitivity in colon cancer cells, significantly suppressed the proliferation of cancer cells, and induced apoptosis. Overexpression of FOSL1 presented the opposite regulatory trend. Mechanistically, FOSL1 activated PHLDA2 and up-regulated its expression. Moreover, by activating glycolysis, PHLDA2 promoted 5-Fu resistance and cell proliferation, and reduced cell apoptosis in colon cancer. Conclusion: Down-regulated FOSL1 expression could enhance the 5-FU sensitivity of colon cancer cells, and FOSL1/PHLDA2 axis may be an effective target for overcoming chemotherapy resistance in colon cancer."

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