Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuchang District, Wuhan, China.
Department of Vascular Surgery, Renmin Hospital of Wuhan University, Wuchang District, Wuhan, China.
J Cell Physiol. 2019 Aug;234(10):18679-18687. doi: 10.1002/jcp.28508. Epub 2019 Apr 16.
Aberrant microRNAs are widely identified in multiple cancers, including lung cancer. miR-135a-5p can function as a significant tumor regulator in diverse cancers via impacting multiple genes in oncogenic pathways. Nevertheless, the biological role of miR-135a-5p in lung cancer is poorly known. Here, we investigated its function in lung cancer. As exhibited, miR-135a-5p was elevated in lung cancer cells in contrast to BEAS-2B cells. Then, we inhibited miR-135a-5p expression by transfecting LV-anti-miR-135a-5p into lung cancer cells. As displayed, miR-135a-5p was obviously reduced in A549 and H1299 cells. Knockdown of miR-135a-5p repressed lung cancer cell growth and cell proliferation. Meanwhile, cell colony formation capacity was depressed, cell apoptosis was enhanced and cell cycle progression was blocked in G1 phase by inhibition of miR-135a-5p in vitro. Additionally, the migration and invasion of A549 and H1299 cells was strongly depressed by LV-anti-miR-135a-5p. For another, by using informatics analysis, lysyl oxidase-like 4 (LOXL4) was speculated as the downstream target of miR-135a-5p. We validated their direct correlation and moreover, overexpression of miR-135a-5p restrained LOXL4 levels in lung cancer cells. Subsequently, we proved that miR-135a-5p promoted lung cancer development via targeting LOXL4 by carrying out the in vivo assays. Taken these together, our study revealed miR-135a-5p might be indicated as a perspective for lung cancer via targeting LOXL4.
异常的 microRNAs 在多种癌症中广泛存在,包括肺癌。miR-135a-5p 可以通过影响致癌途径中的多个基因,在多种癌症中作为重要的肿瘤调节剂发挥作用。然而,miR-135a-5p 在肺癌中的生物学作用知之甚少。在这里,我们研究了它在肺癌中的功能。结果显示,与 BEAS-2B 细胞相比,肺癌细胞中 miR-135a-5p 升高。然后,我们通过转染 LV-anti-miR-135a-5p 抑制肺癌细胞中的 miR-135a-5p 表达。结果显示,A549 和 H1299 细胞中 miR-135a-5p 明显减少。miR-135a-5p 敲低抑制肺癌细胞生长和细胞增殖。同时,体外抑制 miR-135a-5p 可抑制细胞集落形成能力,增强细胞凋亡,阻滞细胞周期于 G1 期。此外,LV-anti-miR-135a-5p 强烈抑制 A549 和 H1299 细胞的迁移和侵袭。另外,通过信息学分析,赖氨酸氧化酶样 4(LOXL4)被推测为 miR-135a-5p 的下游靶标。我们验证了它们的直接相关性,并且过表达 miR-135a-5p 可抑制肺癌细胞中 LOXL4 的水平。随后,我们通过进行体内实验证明,miR-135a-5p 通过靶向 LOXL4 促进肺癌的发展。综上所述,我们的研究表明,通过靶向 LOXL4,miR-135a-5p 可能成为肺癌的一个有前途的治疗靶点。