2. Academic Validation
  3. c-Myc-XRCC2-FOS axis promotes the proliferation and the resistance to Doxorubicin of NSCLC

c-Myc-XRCC2-FOS axis promotes the proliferation and the resistance to Doxorubicin of NSCLC

  • Biomed Pharmacother. 2024 Oct:179:117315. doi: 10.1016/j.biopha.2024.117315.
Peihe Zhang 1,  Hui Li 2,  Han Gong 3,  Yuxuan Tian 1,  Fuxin Chen 4,  Xiang Li 5,  Chunbo Xie 6,  Chaofeng Tu 7,  Siyi Qian 4,  Yueqiu Tan 8,  Qiang Liu 9,  Bin Zhang 10
Affiliations

Affiliations

  • 1 Department of Hepatobiliary and Intestinal Surgery of Hunan Cancer Hospital & the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, Changsha 410013, China.
  • 2 Department of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
  • 3 Department of Hepatobiliary and Intestinal Surgery of Hunan Cancer Hospital & the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
  • 4 Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, Changsha 410013, China.
  • 5 Department of Pathology, Xiangya Medical School, Central South University, Changsha, Hunan, China.
  • 6 Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China.
  • 7 Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China; Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China.
  • 8 Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China; Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China; College of Life Sciences, Hunan Normal University, Changsha, China.
  • 9 Department of Hepatobiliary and Intestinal Surgery of Hunan Cancer Hospital & the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China. Electronic address: 529889432@qq.com.
  • 10 Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, Changsha 410013, China. Electronic address: coolzhangbin22@163.com.
PMID: 39153434 DOI: 10.1016/j.biopha.2024.117315
Abstract

Lung Cancer represents one of the most prevalent malignant neoplasms, commanding an alarming incidence and mortality rate globally. Non-small cell lung Cancer (NSCLC), constituting approximately 80 %-90 % of all lung Cancer cases, is the predominant pathological manifestation of this disease, with a disconcerting 5-year survival rate scarcely reaching 10 %. Extensive prior investigations have elucidated that the aberrant expression of X-ray repair cross-complementing gene 2 (XRCC2), a critical meiotic gene intricately involved in the DNA damage repair process, is intimately associated with tumorigenesis. Nevertheless, the precise roles and underlying mechanistic pathways of XRCC2 in NSCLC remain largely elusive. In the present study, we discerned an overexpression of XRCC2 within NSCLC patient tissues, particularly in high-grade samples, when juxtaposed with normal tissues. Targeted knockdown of XRCC2 notably impeded the proliferation of NSCLC both in vitro and in vivo. Comprehensive RNA Sequencing and flow rescue assays unveiled that XRCC2 augments the proliferation of NSCLC cells through the down-regulation of FOS expression. Moreover, the c-Myc gene was definitively identified as an XRCC2 transcriptional factor by means of chromatin immunoprecipitation (ChIP) and luciferase reporter assays, whereby pharmacological attenuation of c-Myc expression, in conjunction with Doxorubicin, synergistically curtailed NSCLC cell growth both in vitro and in vivo. Collectively, our findings proffer critical insights into the novel c-Myc-XRCC2-FOS axis in promoting both proliferation and resistance to Doxorubicin in NSCLC cells, thereby extending a promising avenue for potential new diagnostic strategies and therapeutic interventions in NSCLC.

Keywords

Doxorubicin resistance; FOS; NSCLC; XRCC2; c-Myc; proliferation.

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