microRNA- 660 Enhances Cisplatin Sensitivity via Decreasing SATB2 Expression in Lung Adenocarcinoma

Genes (Basel). 2023 Apr 14;14(4):911. doi: 10.3390/genes14040911.

Abstract

Increasing evidence suggests that microRNAs' (miRNAs) abnormal expression is one of the main factors of chemotherapy resistance in various cancers. However, the role of miRNAs in lung adenocarcinoma (LUAD) resistance to cisplatin is still unclear. In this study, we analyzed a microarray dataset to investigate miRNAs related to cisplatin resistance in LUAD. The expression of miRNAs in LUAD tissues and cell lines was detected using real-time quantitative polymerase chain reaction (RT-qPCR). Special AT-Rich Sequence-Binding Protein 2 (SATB2) in LUAD cell lines was detected using RT-qPCR and Western blot. Cell proliferation was measured by CCK8 and colony formation assays, while cell cycle and apoptosis were measured by flow cytometry. A dual-luciferase reporter assay was performed to confirm that SATB2 is a target gene of microRNA-660 (miR-660). We showed that the expression of miR-660 was not only decreased in LUAD cells and tissues but also further decreased in the cisplatin-resistant A549 cell line. The overexpression of miR-660 increased cisplatin sensitivity in LUAD cells. In addition, we identified SATB2 as a direct target gene of miR-660. We also revealed that miR-660 increased cisplatin sensitivity in LUAD cells via targeting SATB2. In conclusion, miR-660/SATB2 axis is a key regulator of cisplatin resistance in LUAD.

Keywords: SATB2; cisplatin sensitivity; lung adenocarcinoma; miR-660.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung* / drug therapy
  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / metabolism
  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / genetics
  • Adenocarcinoma* / pathology
  • Cisplatin / pharmacology
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Matrix Attachment Region Binding Proteins* / genetics
  • MicroRNAs* / metabolism
  • Transcription Factors / genetics

Substances

  • Cisplatin
  • MicroRNAs
  • Transcription Factors
  • SATB2 protein, human
  • Matrix Attachment Region Binding Proteins
  • MIRN660 microRNA, human

Grants and funding

This study was supported by grants from the National Science and Technology Support Program of the Ministry of Science and Technology (No. 2015BAI12B08), the National Natural Science Foundation of China (No. 81972773), the Natural Science Foundation of Hunan Province (No. 2022JJ40245), and the Changsha Municipal Natural Science Foundation (kq2014211).