Wang Tao, Zhai Ruiren, Lv Xiuhua, Wang Ke, Xu Junqing
Department of Thoracic Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi'an, 710038, Shaanxi, China.
Department of Tumor Center, Sunshine Union Hospital, Weifang, 261000, Shandong, China.
BMC Pulm Med. 2020 Aug 14;20(1):217. doi: 10.1186/s12890-020-01229-0.
Lung adenocarcinoma (LAD) is a prevalent type of bronchogenic malignant tumor and one of the most critical factors related to human death. Long noncoding RNAs (lncRNAs) are involved in many complex biological processes and have been emerged as extremely important regulators of various cancers. LINC02418, a novel lncRNA, hasn't been mentioned in previous studies on cancer development. Therefore, it's important to define the potential function of LINC02418 in LAD.
Gene expression was examined by RT-qPCR or western blot. CCK-8, colony formation, TUNEL, and transwell assays were utilized to study the role of LINC02418 in LAD. The interaction of miR-4677-3p with LINC02418 (or KNL1) was verified through luciferase reporter, RIP and RNA pull-down assays.
High expression of LINC02418 was observed in LAD specimens and cells. Downregulation of LINC02418 obstructed the proliferation and motility of LAD cells. Moreover, LINC02418 negatively modulated miR-4677-3p expression and miR-4677-3p overexpression could repress cell proliferation and migration. Moreover, kinetochore scaffold 1 (KNL1) expression was negatively modulated by miR-4677-3p but positively regulated by LINC02418. Furthermore, miR-4677-3p could bind with LINC02418 (or KNL1). Finally, KNL1 overexpression reversed the inhibitory function of LINC02418 deficiency in the malignant behaviors of LAD cells.
LINC02418 contributes to the malignancy in LAD via miR-4677-3p/KNL1 signaling, providing a probable therapeutic direction for LAD.
肺腺癌（LAD）是一种常见的支气管源性恶性肿瘤，也是导致人类死亡的最关键因素之一。长链非编码RNA（lncRNAs）参与许多复杂的生物学过程，已成为各种癌症极其重要的调节因子。LINC02418是一种新型lncRNA，在先前关于癌症发展的研究中尚未被提及。因此，明确LINC02418在LAD中的潜在功能具有重要意义。
通过RT-qPCR或蛋白质免疫印迹法检测基因表达。利用CCK-8、集落形成、TUNEL和Transwell实验研究LINC02418在LAD中的作用。通过荧光素酶报告基因、RNA免疫沉淀（RIP）和RNA下拉实验验证miR-4677-3p与LINC02418（或KNL1）的相互作用。
在LAD标本和细胞中观察到LINC02418高表达。LINC02418的下调阻碍了LAD细胞的增殖和运动能力。此外，LINC02418负向调节miR-4677-3p的表达，miR-4677-3p的过表达可抑制细胞增殖和迁移。此外，动粒支架蛋白1（KNL1）的表达受到miR-4677-3p的负向调节，但受到LINC02418的正向调节。此外，miR-4677-3p可与LINC02418（或KNL1）结合。最后，KNL1的过表达逆转了LINC02418缺陷对LAD细胞恶性行为的抑制作用。
LINC02418通过miR-4677-3p/KNL1信号通路促进LAD的恶性发展，为LAD提供了一个可能的治疗方向。
