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

Sep 21, 2026

Lung cancer cells often acquire resistance to cisplatin (DDP) during continuous chemotherapy, limiting treatment efficacy. This study analyzes miR-149-3p levels in lung tissues and cells and evaluates lung cancer cell behaviors using H446/DDP and A549/DDP models. Bioinformatics and confirmation identify TMPRSS4 as a downstream target of miR-149-3p. Western blotting assesses migration, invasion, apoptosis, and TMPRSS4 expression, while a nude-mouse graft model tests tumor growth effects.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

Materials and methods

RESEARCH ARTICLE miR-149-3p targeting TMPRSS4 regulates the sensitivity to cisplatin to inhibit the progression of lung cancer Beibei Qin 1, 2\#, Dongfang Tang 3\#, and Mingzhi Zhang 1 ∗ 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. Keywords: miR-149-3p, lung cancer, TMPRSS4, DDP sensitivity. Introduction Lung cancer, a frequently diagnosed condition, aﬀected 2.2 million people and resulted in 1.8 million deaths worldwide in 2020 [1, 2] . Lung cancer is divided into two major types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) [3, 4] . SCLC accounts for approximately 15% of lung cancer cases, while NSCLC makes up 85% . NSCLC has several subtypes [5, 6] and is highly malignant, progressing rapidly. Consequently, most patients are diagnosed at a late stage, for which chemotherapy, particularly platinum-based treatments, is often the preferred option [7, 8] . However, prolonged use of cis-diamminedichloroplatinum (DDP) in chemotherapy leads to drug resistance in lung cancer cells, reducing its therapeutic eﬃcacy [9, 10] . Thus, enhancing the sensitivity of lung cancer cells to DDP is crucial. MicroRNAs (miRNAs), approximately 22–24 nucleotides long, belong to the category of non-coding RNAs. Many studies have shown that miRNAs play key roles in regulating various cellular processes, including apoptosis, proliferation, and disease progression [11, 12] . miRNAs target speciﬁc genes by basepairing and binding to the target gene’s 3􀀃 -UTR, resulting in mRNA degradation or translation inhibition [13] . Depending on their regulation in tumors, miRNAs can function as oncogenesor tumor suppressors [14] . miR-149-3p, located on chromosome 2q37.3, is encoded by the precursor gene miR-149 . Numerous studies have demonstrated that dysregulation of miR-149-3pis associated with pathological processes in cancer, including tumor cell proliferation, metastasis, and apoptosis [15, 16] . Shenet al. [17] found that miR-149-3p overexpression reduced the proliferation and viability of oralsquamous cell carcinoma cells. Another study [18] demonstrated a link between miR-149-3p and DDP resistance in ovarian cancer cells. However, its role in lung cancer progression and its impact on DDP sensitivity remain unclear. Transmembrane serine protease 4 (TMPRSS4), a type II transmembrane serine protease, is located on chromosome 11q23 .3 (Gene ID: 56649) . It is expressed in several human organs, including the esophagus, stomach, small intestine, colon, bladder, and kidney, though its physiological functi

FAQs

Why is improving cisplatin (DDP) sensitivity important in lung cancer?

Continuous chemotherapy often leads to DDP resistance in lung cancer cells, which reduces therapeutic efficacy. Improving DDP sensitivity is therefore crucial for better treatment outcomes.

What role does miR-149-3p play in lung cancer DDP sensitivity?

miR-149-3p expression is reduced in lung cancer tissues and cells. Overexpression of miR-149-3p inhibits progression, promotes apoptosis, and enhances chemosensitivity to DDP, including in vivo.

How is TMPRSS4 connected to miR-149-3p and the observed cancer effects?

Bioinformatics predicts TMPRSS4 as a downstream target of miR-149-3p, which is confirmed experimentally. miR-149-3p negatively regulates TMPRSS4, reducing malignancy-associated characteristics and further improving DDP sensitivity.

Sep 21, 2026

Upload by Genevieve