He Yiren, Wang Yinfeng, Liu Liu, Liu Shaojun, Liang Lichuan, Chen Yinan, Zhu Zhiqiang
Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, People's Republic of China.
Department of Critical Care Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, People's Republic of China.
Onco Targets Ther. 2020 Jan 31;13:1001-1010. doi: 10.2147/OTT.S228216. eCollection 2020.
There is increasing evidence that circular RNAs (circRNAs) play an important role in human cancers. As a newly identified human circular RNA, circ_0006282 is abnormally expressed in several types of cancers and promotes the development of cancers. However, the expression and function of circ_0006282 in gastric cancer (GC) remain unclear.
The expression of circ_0006282 in cancer tissues and adjacent non-cancer tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR) method, and the relationship between circ_0006282 expression and clinicopathological parameters was analyzed. After knockdown of circ_0006282 by RNA interference in GC cells, CCK-8 assay, colony formation and transwell assays were conducted to examine the effects of circ_0006282 on GC cells. The influence of circ_0006282 on tumor growth in vivo was assessed in a xenograft model. Furthermore, regulatory relationship between circ_0006282, miR-155 and FBXO22 was detected by luciferase assay, qRT-PCR and Western blot.
The expression of circ_0006282 in GC tissues was significantly higher than its adjacent non-cancer tissues and over-expression of circ_0006282 was associated with tumor size, lymph nodes metastasis and TNM stage, but no obvious links with other pathological parameters. Knockdown of circ_0006282 inhibited the proliferation and metastasis ability of GC cells in vitro and suppressed the tumor growth in vivo. Furthermore, mechanistic investigations suggested that circ_0006282 served as a competing endogenous RNA (ceRNA) of miR-155. Moreover, FBXO22 was identified as the functional target of miR-155 and down-expression of circ_0006282 inhibited FBXO22 expression. Rescue assays also demonstrated that the oncogenic function of circ_0006282 is partly attributed to its regulation on miR-155/FBXO22 axis.
Our findings indicated that over-expression of circ_0006282 down‑regulated miR-155 to activate the expression of FBXO22, thus promoting proliferation and metastasis of GC cells, which provides a promising therapeutic target for GC treatment.
越来越多的证据表明，环状RNA（circRNA）在人类癌症中发挥重要作用。作为一种新发现的人类环状RNA，circ_0006282在多种癌症中异常表达，并促进癌症的发展。然而，circ_0006282在胃癌（GC）中的表达和功能仍不清楚。
采用定量实时聚合酶链反应（qRT-PCR）法检测circ_0006282在癌组织和癌旁非癌组织中的表达，并分析circ_0006282表达与临床病理参数之间的关系。在GC细胞中通过RNA干扰敲低circ_0006282后，进行CCK-8检测、集落形成实验和Transwell实验，以检测circ_0006282对GC细胞的影响。在异种移植模型中评估circ_0006282对体内肿瘤生长的影响。此外，通过荧光素酶报告基因检测、qRT-PCR和蛋白质免疫印迹法检测circ_0006282、miR-155和FBXO22之间的调控关系。
circ_0006282在GC组织中的表达显著高于其癌旁非癌组织，circ_0006282的过表达与肿瘤大小、淋巴结转移和TNM分期相关，但与其他病理参数无明显关联。敲低circ_0006282可抑制GC细胞在体外的增殖和转移能力，并抑制体内肿瘤生长。此外，机制研究表明，circ_0006282作为miR-155的竞争性内源性RNA（ceRNA）发挥作用。此外，FBXO22被鉴定为miR-155的功能靶点，circ_0006282的低表达抑制FBXO22的表达。挽救实验还表明，circ_0006282的致癌功能部分归因于其对miR-155/FBXO22轴的调控。
我们的研究结果表明，circ_0006282的过表达下调miR-155以激活FBXO22的表达，从而促进GC细胞的增殖和转移，这为GC治疗提供了一个有前景的治疗靶点。
