1. Academic Validation
  2. MicroRNA-103a-3p potentiates chemoresistance to cisplatin in non-small cell lung carcinoma by targeting neurofibromatosis 1

MicroRNA-103a-3p potentiates chemoresistance to cisplatin in non-small cell lung carcinoma by targeting neurofibromatosis 1

  • Exp Ther Med. 2020 Mar;19(3):1797-1805. doi: 10.3892/etm.2020.8418.
Hongge Zhu 1 Jie Yang 2 Shun'e Yang 3
Affiliations

Affiliations

  • 1 Department of Second Pulmonary Medicine, The Third Hospital Affiliated of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
  • 2 Department of Video Center, The Third Hospital Affiliated of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
  • 3 Department of Lymphoma and Breast Cancer Internal Medicine, The Third Hospital Affiliated of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
Abstract

Lung Cancer remains the leading cause of cancer-associated mortality worldwide, and non-small-cell lung Cancer (NSCLC) contributes to ~80% of these deaths. However, both primary and acquired cisplatin resistance frequently occurs within the disease and represents a huge clinical treatment problem. The underlying molecular mechanisms are not yet completely understood, but in recent years, MicroRNAs (miR) have been reported to play vital roles in the development of lung Cancer and chemoresistance. In the present study, it was revealed that there were increased expression levels of miR-103a-3p in both NSCLC cell lines and human NSCLC samples that exhibited resistance to cisplatin. The results also revealed that the inhibition of miR-103a-3p in A549/cisplatin cells significantly sensitized these cells to cisplatin, while inhibition of miR-103a-3p expression inhibited tumor growth and enhanced the function of cisplatin in a xenograft animal model. Furthermore, the present study demonstrated that miR-103a-3p regulates cisplatin resistance by targeting neurofibromatosis 1 (NF1) via activating ERK signaling in vitro and in vivo. In conclusion, NF1 was identified as a special miR-103a-3p target in the present study, and it was revealed that targeting NF1 via miR-103a-3p may help reverse chemoresistance and provide a biomarker to cisplatin responsiveness in NSCLC.

Keywords

cisplatin resistance; extracellular signal-regulated kinase signaling; microRNA-103a-3p; neurofibromin 1; non-small cell lung carcinoma.

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