miR-140-3P Induces Chemotherapy Resistance in Esophageal Carcinoma by Targeting the NFYA-MDR1 Axis

Appl Biochem Biotechnol. 2023 Feb;195(2):973-991. doi: 10.1007/s12010-022-04139-5. Epub 2022 Oct 18.

Abstract

Esophageal carcinoma (EC) is recognized as the 6th most frequent carcinoma in China, with esophageal squamous cell carcinoma (ESCC) being the predominant histologic type. Currently, chemotherapy is one among the most important therapy modalities for patients with ESCC. However, resistance to chemotherapeutic drugs leads to limited treatment options and poor prognosis. In our study, the analysis of small RNA sequencing and digital gene expression (DGE) profiling was done to recognize the microRNAs (miRNAs) and key genes related with drug resistance in ESCC. It was noticed that the hsa-miRNA-140-3p (miR-140-3p) expression was considerably higher in drug-resistant cells than in sensitive cells. In addition, DGE identified target genes of miR-140-3p might perform key roles in ESCC. Furthermore, this work exhibited that miR-140-3p represents the nuclear transcription factor Y subunit alpha (NFYA) gene by targeting its 3'-untranslated regions. Such an interaction might influence the formation of the transcription factor NFY trimer, which in turn may inhibit the transcription of the multidrug resistance 1 gene and, ultimately, to multidrug resistance in ESCC. The inhibition of miR-140-3p decreased resistance to oxaliplatin in EC. Therefore, miR-140-3p may serve as a molecular marker for treatment response, efficacy, and prognosis of chemotherapy in ESCC patients.

Keywords: Chemotherapy; Gene modulation; Spinal injury; Treatment.

MeSH terms

  • CCAAT-Binding Factor / genetics
  • CCAAT-Binding Factor / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / genetics
  • Esophageal Neoplasms* / metabolism
  • Esophageal Squamous Cell Carcinoma* / drug therapy
  • Esophageal Squamous Cell Carcinoma* / genetics
  • Esophageal Squamous Cell Carcinoma* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Prognosis
  • Transcription Factors / genetics

Substances

  • MicroRNAs
  • Transcription Factors
  • NFYA protein, human
  • CCAAT-Binding Factor
  • Mirn140 microRNA, human