Circular RNA circENTPD7 suppresses the accumulation of PTEN to promote cell proliferation in non-small cell lung cancer

Abstract The oncogenic role of circular RNA ENTPD7 (circENTPD7) in cancer biology has been reported in glioblastoma, while its role in non-small cell lung cancer (NSCLC) is unknown. This study was performed to investigate the involvement of circENTPD7 in NSCLC. NSCLC tissues and paired non-tumor tissues were collected from 64 NSCLC patients and the expression of circENTPD7 and PTEN were determined by RT-qPCR. Expression levels of PTEN protein in these tissue samples were measured by ELISA. The 64 NSCLC patients were subjected to a follow-up study to explore the role of circENTPD7 in predicting the survival of NSCLC. Overexpression of circENTPD7 was achieved in NSCLC cells, and the effects of overexpression of circENTPD7 on the expression of PTEN were measured by RT-qPCR and Western blot at mRNA and protein level, respectively. Cell proliferation was assessed by CCK-8 assay. CircENTPD7 was upregulated in NSCLC and high expression levels of circENTPD7 predicts the poor survival rate of NSCLC cells. In NSCLC tissues, circENTPD7 was inversely correlated with PTEN protein but not mRNA. In NSCLC tissues, overexpression of circENTPD7 resulted in downregulation of PTEN, but did not alter the expression of PTEN mRNA. Cell proliferation analysis showed that overexpression of circENTPD7 promoted the proliferation of NSCLC cells and reduced the inhibitory effects of overexpression of PTEN on cell proliferation. CircENTPD7 may suppress the accumulation of PTEN to promote cell proliferation in NSCLC.

摘要 环状RNA ENTPD7（circENTPD7）的致癌作用已在胶质母细胞瘤的肿瘤生物学研究中被报道，但其在非小细胞肺癌（non-small cell lung cancer, NSCLC）中的作用尚不清楚。本研究旨在探讨circENTPD7在NSCLC中的参与作用。收集64例NSCLC患者的癌组织及配对的癌旁正常组织，通过实时定量聚合酶链反应（RT-qPCR）检测circENTPD7与磷酸酶和张力蛋白同源物（PTEN）的表达水平；采用酶联免疫吸附测定（ELISA）检测上述组织样本中PTEN蛋白的表达水平。对64例NSCLC患者进行随访研究，以探讨circENTPD7在预测NSCLC患者生存情况中的价值。在NSCLC细胞中过表达circENTPD7，分别通过RT-qPCR与蛋白质印迹法（Western blot）检测其对PTEN的mRNA与蛋白表达水平的影响；采用CCK-8法检测细胞增殖情况。研究结果显示，circENTPD7在NSCLC组织中呈高表达，且高表达circENTPD7预示NSCLC患者生存率较低。在NSCLC组织中，circENTPD7的表达与PTEN蛋白水平呈负相关，但与PTEN的mRNA水平无明显关联。在NSCLC细胞中，过表达circENTPD7可下调PTEN蛋白的表达，但不改变PTEN的mRNA水平。细胞增殖实验表明，过表达circENTPD7可促进NSCLC细胞增殖，并削弱PTEN过表达对细胞增殖的抑制作用。综上，circENTPD7可能通过抑制PTEN的积累以促进NSCLC细胞的增殖。