Overexpression of miR-328-5p influences cell growth and migration to promote NSCLC progression by targeting LOXL4.
Overexpression of miR-328-5p influences cell growth and migration to promote NSCLC progression by targeting LOXL4.
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miR-328-5p 过表达影响细胞生长和迁移，通过靶向 LOXL4 促进 NSCLC 进展
DOI：
10.21037/atm-22-345
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发表时间：
2022-03
影响因子：
--
通讯作者：
Zhao, Xiaoshan
中科院分区：
文献类型：
--
作者：
Ji, Yanzhao;You, Yanting;Wu, Yifen;Wang, Min;He, Qiuxing;Zhou, Xinghong;Chen, Liqian;Sun, Xiaomin;Liu, Yanyan;Fu, Xiuqiong;Kwan, Hiu Yee;Zuo, Qiang;Luo, Ren;Zhao, Xiaoshan
背景肺癌是世界范围内癌症相关死亡的主要原因，并且大多数肺癌被分类为非小细胞肺癌（NSCLC）。miR-328影响多种肿瘤的进展，但miR-328- 5 p在NSCLC中的作用尚未阐明。本研究的目的是阐明miR-328- 5 p和赖氨酰氧化酶样4（LOXL 4）在NSCLC中的致癌作用和潜在分子机制。方法采用实时荧光定量聚合酶链反应（qRT-PCR）检测胃癌组织及癌旁组织中miR-328- 5 p的表达。采用慢病毒介导miR-328- 5 p干预NSCLC细胞后，RT-qPCR检测miR-328- 5 p的表达水平。采用CCK-8细胞计数试剂盒、细胞集落形成、流式细胞术、创伤愈合、Transwell法检测NSCLC细胞恶性表型。建立裸鼠皮下肿瘤模型，观察miR-328- 5 p对肿瘤发生的影响。通过包括转录组测序、双荧光素酶和蛋白质印迹测定的综合分析来验证miR-328- 5 p靶向L0 XL 4的3 'UTR。结果在TCGA数据库中的NSCLC细胞和NSCLC患者的肿瘤组织中，miR-328- 5 p的表达水平较高。过表达的miR-328- 5 p促进NSCLC细胞增殖、存活和迁移，并促进体内肿瘤生长。miR-328- 5 p的敲低抑制了肿瘤发生活性。转录组测序分析显示，LOXL 4被miR-328- 5 p下调，这被双荧光素酶报告基因和western-blot分析证实。结论miR-328- 5 p靶向调控LOXL 4促进NSCLC细胞增殖和迁移。
Background Lung cancer is the leading cause of cancer-associated mortality worldwide, and most lung cancers are classified as non-small cell lung cancer (NSCLC). MiR-328 influence the progression of multiple tumors, but the role of miR-328-5p in NSCLC has not been elucidated. The aim of this study was to illuminate the oncogenic role and potential molecular mechanisms of the miR-328-5p and lysyl oxidase like 4 (LOXL4) in NSCLC. Methods Expression of miR-328-5p was detected by real-time quantitative polymerase chain reaction (qRT-PCR) in tumor and non-tumor adjacent tissues. After Lentivirus-miR-328-5p was employed to intervene this miRNA in NSCLC cell lines, RT-qPCR was used to detect the expression levels of miR-328-5p. Cell Counting Kit-8 (CCK-8), cell colony formation, flow cytometry, wound healing, Transwell assays were used to determine the malignant phenotypes of NSCLC cells. Nude mice models of subcutaneous tumors were established to observe the effect of miR-328-5p on tumorigenesis. Targeting the 3'UTR of LOXL4 by miR-328-5p was verified by integrated analysis including transcriptome sequencing, dual-luciferase and western-blot assays. Results High miR-328-5p level was observed in NSCLC cells from The Cancer Genome Atlas (TCGA) database and tumor tissues collected from NSCLC patients. Overexpressed miR-328-5p promoted NSCLC cell proliferation, survival, and migration, and promoted tumor growth in vivo. Knockdown of miR-328-5p suppressed tumorigenic activities. Transcriptome sequencing analysis revealed that LOXL4 was downregulated by miR-328-5p, which was confirmed by dual-luciferase reporter and western-blot assays. Conclusions miR-328-5p showed targeted regulation of LOXL4 to promote cell proliferation and migration in NSCLC.
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影响因子：
20.4
作者：
Smeltzer, Matthew P.;Lee, Yu-Sheng;Div, Nicholas R. Faris M.;Fehnel, Carrie;Akinbobola, Olawale;Meadows-Taylor, Meghan;Spencer, David;Sales, Elizabeth;Okun, Sherry;Giampapa, Christopher;Anga, Amal;Pacheco, Alicia;Ray, Meredith A.;Osarogiagbon, Raymond U.
通讯作者：
Osarogiagbon, Raymond U.
影响因子：
15.9
作者：
Delic, Sabit;Lottmann, Nadine;Riemenschneider, Markus J.
通讯作者：
Riemenschneider, Markus J.
影响因子：
16.2
作者：
Feng, Rui-Mei;Zong, Yi-Nan;Xu, Rui-Hua
通讯作者：
Xu, Rui-Hua
影响因子：
5.6
作者：
Saul, Meike J.;Hegewald, Anett B.;Jakobsson, Per Johan
通讯作者：
Jakobsson, Per Johan
影响因子：
13.6
作者：
Liu, Yang;Fan, Jia;Hu, Tony Y.
通讯作者：
Hu, Tony Y.