ABSTRACT

Non-small cell lung cancer (NSCLC) is a leading cause of cancer death in both men and women. microRNAs (miRs) can exert important functions in cancer development. However, the role of miR-877 in NSCLC as it relates to tartrate resistant acid phosphatase 5 (ACP5) is unknown. For this study, the gain-and-loss-of-function experiments were performed to explore the effects of miR-877 and ACP5 on NSCLC. miR-877 expression in LC and paracancerous tissues, lung epithelial cell line and NSCLC cell lines was detected, and the association between miR-877 expression and clinical features of LC patients was analyzed. The levels of ACP5, epithelial-mesenchymal transition (EMT) markers and apoptosis-related proteins were measured. In vivo experiments were conducted for further validation. Consequently, we found that miR-877 expression was lowered in LC tissues and cell lines, and correlated with clinical stage, differentiation, lymph node metastasis and prognosis of NSCLC patients. Additionally, miR-877 was determined to inhibit ACP5 activity, and miR-877 downregulated the PI3K/AKT pathway by silencing ACP5. Furthermore, overexpression of miR-877 inhibited the viability, migration, invasion and EMT of NSCLC cells, but promoted cell apoptosis. In conclusion, miR-877 overexpression inhibited malignant biological behaviors of NSCLC cells by downregulating ACP5 and inactivating the PI3K/AKT pathway.

摘要

非小细胞肺癌 (NSCLC) 是男性和女性癌症死亡的主要原因。microRNAs (miRs) 可以在癌症发展中发挥重要作用。然而，miR-877 在 NSCLC 中的作用是未知的，因为它与抗酒石酸酸性磷酸酶 5 (ACP5) 相关。在本研究中，进行了功能获得和损失实验以探索 miR-877 和 ACP5 对 NSCLC 的影响。检测 LC 和癌旁组织、肺上皮细胞系和 NSCLC 细胞系中 miR-877 的表达，分析 miR-877 表达与 LC 患者临床特征的相关性。测量了 ACP5、上皮间质转化 (EMT) 标志物和细胞凋亡相关蛋白的水平。体内进行了实验以进一步验证。因此，我们发现 miR-877 在 LC 组织和细胞系中的表达降低，并与 NSCLC 患者的临床分期、分化、淋巴结转移和预后相关。此外，确定 miR-877 抑制 ACP5 活性，并且 miR-877 通过沉默 ACP5 下调 PI3K/AKT 通路。此外，miR-877的过表达抑制了NSCLC细胞的活力、迁移、侵袭和EMT，但促进了细胞凋亡。总之，miR-877过表达通过下调ACP5和失活PI3K/AKT通路来抑制NSCLC细胞的恶性生物学行为。