miR-212-5p exerts tumor promoter function by regulating the Id3/PI3K/Akt axis in lung adenocarcinoma cells
miR-212-5p exerts tumor promoter function by regulating the Id3/PI3K/Akt axis in lung adenocarcinoma cells
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DOI：
10.1002/jcp.29627
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发表时间：
2020-02-10
影响因子：
5.6
通讯作者：
Li, Xiao-jun
中科院分区：
文献类型：
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作者：
Chen, Fang-fang;Sun, Ning;Li, Xiao-jun
microRNA可能作为癌基因或抑癌基因发挥作用，在人类肿瘤发生和癌症发展中起关键作用。越来越多的证据表明，肿瘤抑制因子Id 3参与肿瘤的进展、癌变和肿瘤微环境。我们鉴定了miR-212- 5 p作为Id 3的负转录后调节因子。采用双荧光素酶报告基因分析验证Id 3是miR-212- 5 p的直接靶基因。Id 3在非小细胞肺癌（NSCLC）组织和细胞中呈低表达，而miR-212- 5 p呈高表达。此外，我们发现miR-212- 5 p表达水平较高的NSCLC患者生存时间较短。此外，miR-212- 5 p可直接靶向Id 3，降低其表达。miR-212- 5 p过表达通过逆转Id 3的作用显著加速细胞增殖、迁移和侵袭。Id 3过表达通过沉默miR-212- 5 p表达抑制磷脂酰肌醇3激酶（PI 3 K）/Akt活性，从而促进肺癌细胞的凋亡并抑制细胞增殖。与体外结果一致，使用异种移植小鼠模型来验证miR-212- 5 p可以通过靶向Id 3促进肿瘤发生并在体内也激活PI 3 K/Akt通路的事实。综上所述，本结果表明miR-212- 5 p可能通过靶向Id 3通过PI 3 K/Akt信号通路参与NSCLC的进展。
microRNAs may function as oncogenes or tumor suppressor genes that play crucial roles in human carcinogenesis and cancer development. Growing evidence revealed that the tumor suppressor Id3 is involved in tumor progression, carcinogenesis, and the tumor microenvironment. We identified miR-212-5p as a negative posttranscriptional modulator of Id3. Dual luciferase reporter assay was used to verify that Id3 is a direct target gene of miR-212-5p. Id3 was lowly expressed and miR-212-5p was highly expressed in non-small-cell lung cancer (NSCLC) tissues and cells. In addition, we found that NSCLC patients having a higher level of miR-212-5p expression had a shorter survival time. Besides this, miR-212-5p could directly target Id3 and reduce its expression. miR-212-5p overexpression significantly accelerated cell proliferation, migration, and invasion by reversing the effects of Id3. Id3 overexpression by silencing miR-212-5p expression suppressed phosphatidylinositol 3 kinase (PI3K)/Akt activity and consequently promoted apoptosis and inhibited cell proliferation in lung cancer cells. Consistent with the in vitro results, a xenograft mouse model was used to validate the fact that miR-212-5p could promote tumorigenesis by targeting Id3 and activate the PI3K/Akt pathway in vivo as well. Taken together, the present results indicated that miR-212-5p may be involved in progression of NSCLC through the PI3K/Akt signaling pathway by targeting Id3.