Bu Wenjin, Luo Tianyou
1 Chongqing Medical University , Chongqing, China .
2 Department of Ultrasonic Medicine, Inner Mongolia People's Hospital , Hohhot, China .
DNA Cell Biol. 2017 Nov;36(11):976-982. doi: 10.1089/dna.2017.3886. Epub 2017 Sep 5.
Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a lipid and protein phosphatase and possesses an antitumor effect in lung cancers. miRNAs are reportedly abnormally expressed in human lung cancers. However, whether miRNA contributes to PTEN expression in non-small cell lung cancers (NSCLCs) has not been clearly clarified. In the present study, we found that miR-1297 probably binds with 3'UTR sequence of PTEN and negatively regulated the levels of PTEN in NSCLC cells. First, the expression levels of PTEN and Skp2 were detected by western blotting in NSCLC specimens and paired normal tissue specimens. The results showed that decreased levels of PTEN were detected in NSCLC tissues, compared with paired control tissues (**p < 0.01). The expression levels of PTEN were conversely correlated with the levels of Skp2 in clinical NSCLC specimens and NSCLC cell line. Transfection with miR-1297 mimic significantly promoted cell viability of A549 cells and NCI-H460 cells by downregulating the level of PTEN and upregulating the expression of Skp2. Interestingly, knockdown of Skp2 did not affect the expression of PTEN in A549 cells. Thus, miR-1297 might work as an oncogene by regulating PTEN/Akt/Skp2 signaling pathway in NSCLC cells. PTEN and Skp2 might be the potential targets in the clinical therapy of lung cancers.
第10号染色体缺失的磷酸酶及张力蛋白同源物(PTEN)是一种脂质和蛋白质磷酸酶,在肺癌中具有抗肿瘤作用。据报道,miRNA在人类肺癌中异常表达。然而,miRNA是否在非小细胞肺癌(NSCLC)中影响PTEN的表达尚未明确阐明。在本研究中,我们发现miR-1297可能与PTEN的3'UTR序列结合,并负向调节NSCLC细胞中PTEN的水平。首先,通过蛋白质免疫印迹法检测NSCLC标本及配对的正常组织标本中PTEN和Skp2的表达水平。结果显示,与配对的对照组织相比,NSCLC组织中PTEN水平降低(**p < 0.01)。在临床NSCLC标本和NSCLC细胞系中,PTEN的表达水平与Skp2的水平呈负相关。转染miR-1297模拟物可通过下调PTEN水平和上调Skp2表达,显著促进A549细胞和NCI-H460细胞的活力。有趣的是,敲低Skp2并不影响A549细胞中PTEN的表达。因此,miR-1297可能通过调节NSCLC细胞中的PTEN/Akt/Skp2信号通路发挥癌基因作用。PTEN和Skp2可能是肺癌临床治疗中的潜在靶点。