Regulation of MicroRNA-497-Targeting AKT2 Influences Tumor Growth and Chemoresistance to Cisplatin in Lung Cancer.
Regulation of MicroRNA-497-Targeting AKT2 Influences Tumor Growth and Chemoresistance to Cisplatin in Lung Cancer.
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靶向 AKT2 的 MicroRNA-497 的调节影响肺癌中的肿瘤生长和顺铂化疗耐药性
DOI：
10.3389/fcell.2020.00840
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发表时间：
2020
影响因子：
5.5
通讯作者：
Jiang BH
中科院分区：
文献类型：
--
作者：
Wang L;Ji XB;Wang LH;Qiu JG;Zhou FM;Liu WJ;Wan DD;Lin MC;Liu LZ;Zhang JY;Jiang BH
MicroRNA-497（miR-497）与多种癌症有关。越来越多的研究表明AKT 2作为一种癌基因在肿瘤中的作用，通过增强癌细胞的存活、迁移和侵袭，与肿瘤的侵袭性密切相关。然而，miR-497/AKT 2轴在非小细胞肺癌（NSCLC）中的作用尚不清楚。方法采用实时荧光定量PCR（qRT-PCR）方法检测miR-497及其靶基因的表达。通过体外和体内试验（细胞增殖试验、细胞迁移试验、集落形成试验、流式细胞术试验、免疫印迹和肿瘤发生试验）研究miR-497在肺癌中的功能。进行荧光素酶报告基因测定以确认miR-497的靶基因。结果在本研究中，我们发现miR-497在肺癌患者的肿瘤组织和血液样本中显著下调。为了了解miR-497抑制肿瘤生长的潜在机制，我们发现miR-497阻断了AKT 2的激活，并通过抑制AKT 2来调节细胞增殖、细胞迁移、集落形成，并增加H1299细胞对顺铂的化疗敏感性。MiR-497还在小鼠异种移植肿瘤中抑制肿瘤生长并在蛋白质和mRNA水平上抑制AKT 2的表达。结论miR-497通过靶向AKT 2抑制肿瘤生长，miR-497/AKT 2轴是NSCLC潜在的治疗靶点。
Background MicroRNA-497 (miR-497) has been implicated in several cancers. Increasing studies demonstrate the role of AKT2 in cancers as an oncogene which is closely associated with tumor aggressiveness by enhancing cancer cell survival, migration and invasion However, miR-497/AKT2 axis in non-small cell lung cancer (NSCLC) remains unclear. Methods Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of miR-497 and its target gene. The function of miR-497 in lung cancer was investigated through in vitro and in vivo assays (cell proliferation assay, cell migration assay, colony formation assay, flow cytometry assay, immunoblotting and tumorigenesis assay). Luciferase reporter assay was conducted to confirm the target gene of miR-497. Results In this study, we found that miR-497 was significantly downregulated in tumor tissues and blood samples of lung cancer patients. To understand the potential mechanism of miR-497 in inhibiting tumor growth, we showed that miR-497 blocked the activation of AKT2 and regulated cell proliferation, cell migration, colony formation and increases chemosensitivity of H1299 cells to cisplatin by inhibiting AKT2. MiR-497 also inhibited tumor growth and suppressed expression of AKT2 at the protein and mRNA levels in mouse xenograft tumors. Conclusion Taken together, our findings indicated that miR-497 suppresses the tumor growth by targeting AKT2, and the miR-497/AKT2 axis is a potential therapeutic target for NSCLC intervention.