LINC00638通过调控miR-541-3p/胰岛素受体底物1/磷脂酰肌醇-3-激酶/蛋白激酶B轴促进非小细胞肺癌进展。
LINC00638 promotes the progression of non-small cell lung cancer by regulating the miR-541-3p/IRS1/PI3K/Akt axis.
作者信息
Zhang Juan, Mou Yanhua, Li Hui, Shen Hui, Song Jun, Li Qingfeng
机构信息
Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei, China.
Institute of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science Hubei University of Arts and Science, Xiangyang 441021, Hubei, China.
出版信息
Heliyon. 2023 Jun 15;9(6):e16999. doi: 10.1016/j.heliyon.2023.e16999. eCollection 2023 Jun.
BACKGROUND
Preceding works reveal the function of long non-coding RNAs (abbreviated to lncRNAs) during non-small cell lung cancer (NSCLC) evolvement. We explored the profile and biological functions of the lncRNA LINC00638 in NSCLC.
METHODS
Reverse transcription-quantitative PCR examined LINC00638 level in NSCLC and corresponding non-tumor tissues, human normal lung epithelial cells BEAS-2B, and NSCLC cells (NCI-H460, HCC-827, A549, H1299, H1975, H460). The gain- and loss-of-function assay of LINC00638 ascertained its function in modulating the proliferation, apoptosis, and invasion of NSCLC cells (HCC-827 and H460). Bioinformatics analysis investigated the underlying mechanisms. Dual luciferase reporter gene and RNA immunoprecipitation (RIP) checked the interactions between LINC00638 and microRNA (miR)-541-3p, miR-541-3p and insulin receptor substrate 1 (IRS1).
RESULTS
LINC00638 was upregulated in NSCLC tissues by contrast to the profiles found in the corresponding non-tumor normal tissues, as well as in NSCLC cells vis-à-vis BEAS-2B cells. LINC00638 upregulation pertained to the poorer survival rates of NSCLC patients. Overexpressing LINC00638 augmented NSCLC cells' proliferation, growth, migration, and invasion but inhibited their apoptosis, while down-regulating LINC00638 led to the opposite. miR-541-3p might be an underlying target of LINC00638, which targeted IRS1, inhibited NSCLC progression, and reversed the carcinogenic effects of LINC00638. Mechanistically, LINC00638/miR-541-3p regulated the IRS1/phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Repressing IRS1/2 using its inhibitor NT157 repressed LINC00638-mediated oncogenic effects.
CONCLUSION
LINC00638 may function as an oncogene in NSCLC by modulating the miR-541-3p/IRS1/PI3K/Akt axis.
背景
先前的研究揭示了长链非编码RNA（lncRNA）在非小细胞肺癌（NSCLC）发展过程中的作用。我们探究了lncRNA LINC00638在NSCLC中的表达谱及生物学功能。
方法
采用逆转录定量PCR检测NSCLC组织及相应的非肿瘤组织、人正常肺上皮细胞BEAS-2B和NSCLC细胞（NCI-H460、HCC-827、A549、H1299、H1975、H460）中LINC00638的水平。对LINC00638进行功能获得和功能缺失实验，以确定其在调节NSCLC细胞（HCC-827和H460）增殖、凋亡和侵袭中的作用。通过生物信息学分析探究潜在机制。采用双荧光素酶报告基因实验和RNA免疫沉淀（RIP）实验检测LINC00638与微小RNA（miR）-541-3p、miR-541-3p与胰岛素受体底物1（IRS1）之间的相互作用。
结果
与相应的非肿瘤正常组织相比，LINC00638在NSCLC组织中上调，与BEAS-2B细胞相比，在NSCLC细胞中也上调。LINC00638上调与NSCLC患者较差的生存率相关。过表达LINC00638可增强NSCLC细胞的增殖、生长、迁移和侵袭能力，但抑制其凋亡，而下调LINC00638则产生相反的效果。miR-541-3p可能是LINC00638的潜在靶点，其靶向IRS1，抑制NSCLC进展，并逆转LINC00638的致癌作用。机制上，LINC00638/miR-541-3p调节IRS1/磷脂酰肌醇3激酶（PI3K）/Akt信号通路。使用其抑制剂NT157抑制IRS1/2可抑制LINC00638介导的致癌作用。
结论
LINC00638可能通过调节miR-541-3p/IRS1/PI3K/Akt轴在NSCLC中发挥癌基因作用。
Zotero 插件