Table_5_MicroRNA-486-5p Suppresses Lung Cancer via Downregulating mTOR Signaling In Vitro and In Vivo.doc

Lung cancer is one of the central causes of tumor-related deaths globally, of which non-small cell lung cancer (NSCLC) takes up about 85%. As key regulators of various biological processes, microRNAs (miRNAs) have been verified as crucial factors in NSCLC. To elucidate the role of miR-486-5p in the mTOR pathway, we investigated its role in NSCLC and related signaling. Our results confirmed that miR-486-5p was downregulated in most of human NSCLC tissue samples and cell lines. Further study confirmed that it inhibited NSCLC through repression of the mTOR pathway via targeting both ribosomal proteins S6 kinase A1 (RPS6KA1, RSK) and ribosomal proteins S6 kinase B1 (RPS6KB1, p70S6K), which are critical components of the mTOR signaling. Additionally, miR-486-5p impeded tumor growth in vivo and inhibited tumor metastasis through repression of the epithelial-mesenchymal transition (EMT). Taken together, our study verified the role that miR-486-5p exerts in NSCLC, and its expression pattern in the different stages and morphologies of NSCLC makes it a promising biomarker in the early diagnosis of the disease.

肺癌是全球范围内肿瘤相关死亡的核心诱因之一，其中非小细胞肺癌（non-small cell lung cancer, NSCLC）占比约85%。微小RNA（microRNAs, miRNAs）作为多种生物学过程的关键调控因子，已被证实是非小细胞肺癌发生发展中的重要因素。为阐明miR-486-5p在mTOR通路中的作用，本研究探讨了其在非小细胞肺癌及相关信号通路中的功能。研究结果证实，miR-486-5p在多数人类非小细胞肺癌组织样本与细胞系中呈低表达。进一步研究确认，其通过靶向mTOR信号通路的关键组分——核糖体蛋白S6激酶A1（ribosomal proteins S6 kinase A1, RPS6KA1，RSK）与核糖体蛋白S6激酶B1（ribosomal proteins S6 kinase B1, RPS6KB1，p70S6K），抑制mTOR通路活性，从而发挥对非小细胞肺癌的抑制作用。此外，miR-486-5p可通过抑制上皮间质转化（epithelial-mesenchymal transition, EMT）在体内阻碍肿瘤生长并抑制肿瘤转移。综上，本研究验证了miR-486-5p在非小细胞肺癌中的作用，且其在非小细胞肺癌不同分期与分型中的表达模式，使其成为该疾病早期诊断的潜在生物标志物。