Zou Aimei, Liu Xingli, Mai Zongjiong, Zhang Junke, Liu Zhuohuan, Huang Qilu, Wu Aibing, Zhou Chenyu
Department of Oncology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan 528308, P.R. China.
Area 7 of Tumor Chemotherapy Department, Central Hospital of Guangdong Nongken, Zhanjiang 524001, P.R. China.
Mol Ther Nucleic Acids. 2019 Sep 6;17:563-577. doi: 10.1016/j.omtn.2019.06.003. Epub 2019 Jun 15.
Long non-coding RNAs and microRNAs (miRNAs) have been reported to participate in the progression of non-small-cell lung cancer (NSCLC). Long intergenic non-protein-coding RNA 472 (LINC00472), miR-149-3p, and miR-4270 were found to be involved in tumor activities, suggesting potential roles in NSCLC. Thus, this study aimed to examine the ability of LINC00472 to influence the progression of NSCLC with the involvement of miR-149-3p and miR-4270. Initially, differentially expressed long non-coding RNAs (lncRNAs), downstream regulatory miRNAs, and genes related to NSCLC were identified. Next, the interaction among LINC00472, miR-149-3p and miR-4270, and KLLN and the p53-signaling pathway was determined. The effect of LINC00472 on the expression of E-cadherin, N-cadherin, and Vimentin was examined through gain-of-function and loss-of-function experiments. Lastly, the effects of LINC00472 on NSCLC tumor growth were assessed in vivo. LINC00472 and KLLN were found to exhibit low levels, while miR-149-3p and miR-4270 were highly expressed in NSCLC. In addition, the overexpression of LINC00472 was observed to upregulate KLLN and activate the p53-signaling pathway, which ultimately inhibited the invasion, migration, and EMT of NSCLC cells via miR-149-3p and miR-4270, corresponding to decreased N-cadherin and Vimentin and increased E-cadherin. The overexpression of LINC00472 exerted an inhibitory effect on tumor growth in vivo. Taken together, the key evidence suggests that the overexpression of LINC00472 can downregulate miR-149-3p and miR-4270 to upregulate KLLN and activate the p53-signaling pathway, thus inhibiting the development of NSCLC. This study highlights the potential of LINC00472 as a promising therapeutic target for NSCLC treatment.
据报道，长链非编码RNA和微小RNA（miRNA）参与了非小细胞肺癌（NSCLC）的进展。发现长链基因间非编码RNA 472（LINC00472）、miR-149-3p和miR-4270参与肿瘤活动，提示其在NSCLC中具有潜在作用。因此，本研究旨在探讨LINC00472在miR-149-3p和miR-4270参与下影响NSCLC进展的能力。首先，鉴定了与NSCLC相关的差异表达长链非编码RNA（lncRNA）、下游调控miRNA和基因。接下来，确定了LINC00472、miR-149-3p和miR-4270以及KLLN与p53信号通路之间的相互作用。通过功能获得和功能丧失实验检测LINC00472对E-钙黏蛋白、N-钙黏蛋白和波形蛋白表达的影响。最后，在体内评估LINC00472对NSCLC肿瘤生长的影响。发现LINC00472和KLLN在NSCLC中表达水平较低，而miR-149-3p和miR-4270高表达。此外，观察到LINC00472的过表达上调了KLLN并激活了p53信号通路，最终通过miR-149-3p和miR-4270抑制了NSCLC细胞的侵袭、迁移和上皮-间质转化，表现为N-钙黏蛋白和波形蛋白减少，E-钙黏蛋白增加。LINC00472的过表达在体内对肿瘤生长具有抑制作用。综上所述，关键证据表明LINC00472的过表达可下调miR-149-3p和miR-4270，上调KLLN并激活p53信号通路，从而抑制NSCLC的发展。本研究突出了LINC00472作为NSCLC治疗有前景治疗靶点的潜力。
