Luo Jia, Xu Lu-Ning, Zhang Sheng-Jun, Jiang Yi-Gui, Zhuo De-Xiang, Wu Lian-Hui, Jiang Xiang, Huang Yue
a Department of Gastroenterology , The Sanming First Hospital Affiliated to Fujian Medical University , Sanming , China.
b Department of Pharmacy , The Sanming First Hospital Affiliated to Fujian Medical University , Sanming , China.
Scand J Gastroenterol. 2018 Jan;53(1):38-45. doi: 10.1080/00365521.2017.1392597. Epub 2017 Oct 26.
Using microarray analysis, we previously showed that many lncRNAs are differentially expressed in colorectal cancer (CRC) tissues compared with normal tissues, suggesting that lncRNAs may be involved the initiation and progression of CRC. In this study, we investigated the expression and function of lncRNA-RP11-317J10.2 in human CRC tissues and cell lines.
LncRNA-RP11-317J10.2 expression level was analyzed in 52 colon cancer and cell lines. We used shRNA to knock-down the expression of RP11-317J10.2, and then proliferation assay, colony formation assay, Boyden chamber assay, FACS and Kaplan-Meier survival analysis were performed to explore the biological effect of RP11-317J10.2. Cyclin D1 protein level was detected by Western blot.
LncRNA-RP11-317J10.2 is downregulated in CRC and decreased expression is significantly associated with advanced tumor stage, larger tumor size and poor prognosis. RNA interference-mediated knockdown of lncRNA-RP11-317J10.2 in CRC cells promotes G1-to-S cell cycle transition, enhances invasiveness and facilitates cell growth in vitro and in mouse tumor xenograft models. Cyclin D1 was upregulated by lncRNA-RP11-317J10.2 knockdown, and co-expression of cyclin D1-targeting siRNA abrogates the pro-tumorigenic effects of lncRNA-RP11-317J10.2 knockdown.
This study reveals a crucial role for lncRNA-RP11-317J10.2 in CRC growth and invasion via upregulation of cyclin D1 expression and suggests that expression of this lncRNA may be a potential prognostic biomarker for CRC.
我们之前通过微阵列分析表明，与正常组织相比，许多长链非编码RNA（lncRNA）在结直肠癌（CRC）组织中差异表达，这表明lncRNA可能参与CRC的发生和发展。在本研究中，我们调查了lncRNA-RP11-317J10.2在人CRC组织和细胞系中的表达及功能。
分析了52例结肠癌组织和细胞系中lncRNA-RP11-317J10.2的表达水平。我们使用短发夹RNA（shRNA）敲低RP11-317J10.2的表达，然后进行增殖试验、集落形成试验、博伊登小室试验、流式细胞术和卡普兰-迈耶生存分析，以探讨RP11-317J10.2的生物学效应。通过蛋白质免疫印迹法检测细胞周期蛋白D1的蛋白水平。
lncRNA-RP11-317J10.2在CRC中表达下调，其表达降低与肿瘤晚期、肿瘤体积较大及预后不良显著相关。RNA干扰介导的CRC细胞中lncRNA-RP11-317J10.2敲低促进G1期到S期的细胞周期转变，增强侵袭性，并在体外和小鼠肿瘤异种移植模型中促进细胞生长。lncRNA-RP11-317J10.2敲低使细胞周期蛋白D1上调，且共表达靶向细胞周期蛋白D1的小干扰RNA可消除lncRNA-RP11-317J10.2敲低的促肿瘤作用。
本研究揭示了lncRNA-RP11-317J10.2通过上调细胞周期蛋白D1的表达在CRC生长和侵袭中起关键作用，并表明该lncRNA的表达可能是CRC的一种潜在预后生物标志物。
