2. Academic Validation
  3. Hsa-miR-4271 downregulates the expression of constitutive androstane receptor and enhances in vivo the sensitivity of non-small cell lung cancer to gefitinib

Hsa-miR-4271 downregulates the expression of constitutive androstane receptor and enhances in vivo the sensitivity of non-small cell lung cancer to gefitinib

  • Pharmacol Res. 2020 Nov;161:105110. doi: 10.1016/j.phrs.2020.105110.
Chunzhan Wang 1,  Shengguang Ding 2,  Baisheng Sun 3,  Liang Shen 4,  Ling Xiao 5,  Zhihai Han 6,  Haitao Huang 7
Affiliations

Affiliations

  • 1 Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Nantong University, Nantong City 226001, Jiangsu Province, PR China; Pulmonary and Crical Care Medecine Department, The 6thMedical Center of PLA General Hospital, Beijing 100048, PR China. Electronic address: [email protected].
  • 2 Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Nantong University, Nantong City 226001, Jiangsu Province, PR China. Electronic address: [email protected].
  • 3 Emergency Department, The Fifth Medical Center of the General Hospital of the Chinese People's Liberation Army, Beijing 100071, PR China. Electronic address: [email protected].
  • 4 Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Nantong University, Nantong City 226001, Jiangsu Province, PR China. Electronic address: [email protected].
  • 5 Department of Internal Medicine, Minhai Hospital, Xiamen City 361100, Fujian Province, PR China. Electronic address: [email protected].
  • 6 Pulmonary and Crical Care Medecine Department, The 6thMedical Center of PLA General Hospital, Beijing 100048, PR China. Electronic address: [email protected].
  • 7 Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Nantong University, Nantong City 226001, Jiangsu Province, PR China. Electronic address: [email protected].
PMID: 32755614 DOI: 10.1016/j.phrs.2020.105110
Abstract

The efficacy of molecular targeting agents is dependent on the metabolism or nuclear receptor-mediated clearance of chemotherapy resistance-related factors such as Cytochrome P450 (CYP) or ATP binding cassette subfamily B member 1 (ABCB1). In this study, we revealed the roles of the microRNA-4271/CAR (constitutive androstane receptor) axis in the regulation of the resistance to molecular Anticancer targeting agents in non-small cell lung Cancer (NSCLC) cells including two main categories of NSCLC: lung adenocarcinoma (AC) and large cell lung Cancer (LCC). The expression of miR-4271 was negatively correlated with CAR expression in NSCLC tissues. MiR-4271 targeted CAR and inhibited the activation of the CAR signaling pathway. Overexpression of CAR in NSCLC enhanced the resistance of NSCLC cells to molecular targeting agents and miR-4271-infected NSCLC cells enhanced their sensitivity to molecular targeting agents such as Gefitinib. The mechanism-data showed that overexpression of miR-4271 decelerated the mechanism or the clearance of molecular targeting agents by targeting the 3'UTR (3' un-translation region). These results suggest that miR-4271 may contribute to the development of more effective strategies for the treatment of advanced NSCLC.

Keywords

Constitutive androstane receptor; Molecular targeting agents; Non-Small cell lung cancer; microRNA-4271.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-103243
    98.67%, Bcl-2 Family Inhibitor