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Abstract：
As one of the most aggressive malignancies, non-small cell lung carcinoma (NSCLC) has high risks of death. It has been demonstrated that circRNAs accelerate NSCLC progression, but the underlying molecular mechanisms of circRNAs in NSCLC were still obscure. In the first place, the circRNA microarray of NSCLC was investigated in this study, and hsa_circ_0008003 (circ-0008003) was chosen as the research object. Then, it was unveiled that the expression of circ-0008003 examined via qRT-PCR was elevated in tumour tissues relative to the non-tumour tissues, which was associated with TNM stage and lymphatic metastasis in NSCLC. Additionally, the prognosis of NSCLC patients with high circ-0008003 level was poor. Besides, circ-0008003 silencing dampened the invasion and proliferation of NSCLC cells. Next, according to the mechanistic studies, circ-0008003 functioned as a ceRNA of ZNF281 in NSCLC by acting as the endogenous sponge for miR-488, which was proved to be a tumour suppressor in NSCLC. Additionally, ZNF281 overexpression and miR-488 suppression recovered the influences of repressed circ-0008003 on NSCLC cellular processes. It was validated in this research that circ-0008003 triggered tumour formation in NSCLC, which was adjusted via miR-488/ZNF281 axis, casting a novel light on the resultful target for treating NSCLC and predicting the prognosis.
摘要：
作为最具侵袭性的恶性肿瘤之一，非小细胞肺癌（NSCLC）具有很高的死亡风险。已经证明circRNAs加速NSCLC进展，但NSCLC中circRNAs的潜在分子机制仍不清楚。首先,在这项研究中研究了NSCLC的circRNA微阵列，并选择hsa_circ_0008003(circ-0008003)作为研究对象。然后，揭示了通过qRT-PCR检测的circ-0008003的表达在肿瘤组织中相对于非肿瘤组织升高，与NSCLC的TNM分期和淋巴结转移有关。此外,高circ-0008003水平的NSCLC患者预后较差。此外,circ-0008003沉默抑制NSCLC细胞的侵袭和增殖。接下来,根据机械研究，circ-0008003通过充当miR-488的内源性海绵而在NSCLC中充当ZNF281的ceRNA，miR-488被证明是NSCLC中的肿瘤抑制剂。此外,ZNF281过表达和miR-488抑制恢复了抑制的circ-0008003对NSCLC细胞过程的影响。在这项研究中验证了circ-0008003在非小细胞肺癌中触发了肿瘤形成，通过miR-488/ZNF281轴调整，为NSCLC的治疗和预测预后提供了新的思路。
