Qin Beibei, Tang Dongfang, Zhang Mingzhi
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China; Department of Oncology, LuoYang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan Province, China.
Department of Thoracic Surgery, Huadong Hospital Affiliated to Fudan University, Jing 'an District, Shanghai, China.
Biomol Biomed. 2024 Dec 11;25(1):165-176. doi: 10.17305/bb.2024.11163.
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.
在持续化疗过程中，肺癌细胞往往会对顺铂（DDP）产生耐药性，因此提高DDP敏感性以增强治疗效果至关重要。分析了肺组织和细胞中miR-149-3p的水平以及肺癌细胞的生物学行为。建立了H446/DDP和A549/DDP细胞系，以研究miR-149-3p如何影响肺癌细胞对DDP的敏感性。生物信息学分析预测跨膜丝氨酸蛋白酶4（TMPRSS4）是miR-149-3p的下游靶点，随后得到证实。采用蛋白质印迹分析检测与迁移、侵袭、凋亡相关的蛋白质以及TMPRSS4的表达。此外，还建立了裸鼠皮下移植瘤模型，以评估miR-149-3p对肿瘤生长的影响。在肺癌组织和细胞中，miR-149-3p表达降低，而TMPRSS4表达升高。miR-149-3p的过表达抑制了癌症进展，促进了凋亡，并增强了肺癌细胞对DDP的化学敏感性。此外，miR-149-3p负向调节TMPRSS4，降低了肺癌细胞的恶性相关特征，并进一步提高了它们对DDP的敏感性。在体内，高表达的miR-149-3p增加了癌细胞的化学敏感性。总之，miR-149-3p通过直接下调TMPRSS4抑制肺癌的侵袭性进展，并增强肺癌细胞对DDP的反应性。
