1. Academic Validation
  2. miR-149-3p targeting TMPRSS4 regulates the sensitivity to cisplatin to inhibit the progression of lung cancer

miR-149-3p targeting TMPRSS4 regulates the sensitivity to cisplatin to inhibit the progression of lung cancer

  • Biomol Biomed. 2024 Oct 1. doi: 10.17305/bb.2024.11163.
Beibei Qin 1 Dongfang Tang 2 Mingzhi Zhang 3
Affiliations

Affiliations

  • 1 Department of Oncology, LuoYang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan Province, China.
  • 2 Department of Thoracic Surgery, Huadong Hospital Affiliated to Fudan University, Jing 'an District, Shanghai, China.
  • 3 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
Abstract

Lung Cancer cells tend to develop resistance to cisplatin (DDP) during continuous chemotherapy, making it crucial to improve DDP sensitivity to enhance therapeutic outcomes. The levels of miR-149-3p in lung tissues and cells, as well as the biological behaviors of lung Cancer cells, were analyzed. H446/DDP and A549/DDP cell lines were established to investigate how miR-149-3p affects lung Cancer cells' sensitivity to DDP. Bioinformatics analysis predicted transmembrane serine protease 4 (TMPRSS4) as a downstream target of miR-149-3p, which was subsequently confirmed. Western blot analysis was used to examine proteins related to migration, invasion, Apoptosis, and TMPRSS4 expression. Additionally, a subcutaneous graft tumor model in nude mice was created to assess the impact of miR-149-3p on tumor growth. In lung Cancer tissues and cells, miR-149-3p expression was reduced, while TMPRSS4 expression was elevated. Overexpression of miR-149-3p inhibited Cancer progression, promoted Apoptosis, and enhanced the chemosensitivity of lung Cancer cells to DDP. Moreover, miR-149-3p negatively regulated TMPRSS4, reducing malignancy-associated characteristics of lung Cancer cells and further improving their DDP sensitivity. In vivo, high miR-149-3p expression increased the chemosensitivity of Cancer cells. In conclusion, miR-149-3p suppresses the aggressive progression of lung Cancer by directly downregulating TMPRSS4 and enhances the responsiveness of lung Cancer cells to DDP.

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