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癌症易感性候选基因9的沉默抑制胃癌并逆转化疗耐药性。

Silence of cancer susceptibility candidate 9 inhibits gastric cancer and reverses chemoresistance.

作者信息

Shang Chao, Sun Lin, Zhang Jiale, Zhao Bochao, Chen Xiuxiu, Xu Huimian, Huang Baojun

机构信息

Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, 110001, China.

Department of Surgical Oncology, First Affiliated Hospital, China Medical University, Shenyang, 110004, China.

出版信息

Oncotarget. 2017 Feb 28;8(9):15393-15398. doi: 10.18632/oncotarget.14871.

Abstract

Cancer Susceptibility Candidate 9 (CASC9) is a novel gene generating long non-coding RNA (lncRNA) with oncogenic potential that was first identified in esophageal cancer. In this study, we have found that CASC9 was overexpressed in gastric cancer (GC) compared to normal gastric tissue. A higher expression level was associated with aggressive pathological characteristics, including deep invasion, poor differentiation and lymph node metastases. In two gastric cancer cell lines, BGC823 and SGC7901, CASC9 were both overexpressed compared to that of normal gastric epithelial cell (GES-1). Moreover, the expression of CASC9 was even higher in BGC823/DR and SGC7901/DR cells that are resistant to paclitaxel or adriamycin. CASC9 knockdown inhibited proliferation and promoted cell apoptosis In BGC823/DR and SGC7901/DR cells. The invasion potential was also significantly inhibited measured by Transwell assay. In addition, CASC9 knockdown in BGC823/DR and SGC7901/DR cells restored chemosensitivity to paclitaxel and adriamycin. This was associated with decreased expression of multidrug resistance 1 (MDR1) protein. Taken together, our data suggest that expression of lncRNA CASC9 correlated with aggressive pathological characteristics of GC, it may serve as a potential oncogene to regulate proliferation, invasion, and chemoresistance of GC cells.

摘要

癌症易感性候选基因9(CASC9)是一种可产生具有致癌潜力的长链非编码RNA(lncRNA)的新型基因,最初在食管癌中被鉴定出来。在本研究中,我们发现与正常胃组织相比,CASC9在胃癌(GC)中过表达。较高的表达水平与侵袭性病理特征相关,包括深度浸润、低分化和淋巴结转移。在两种胃癌细胞系BGC823和SGC7901中,与正常胃上皮细胞(GES-1)相比,CASC9均过表达。此外,在对紫杉醇或阿霉素耐药的BGC823/DR和SGC7901/DR细胞中,CASC9的表达甚至更高。在BGC823/DR和SGC7901/DR细胞中,敲低CASC9可抑制细胞增殖并促进细胞凋亡。通过Transwell实验检测,侵袭能力也显著受到抑制。此外,在BGC823/DR和SGC7901/DR细胞中敲低CASC9可恢复对紫杉醇和阿霉素的化学敏感性。这与多药耐药蛋白1(MDR1)表达降低有关。综上所述,我们的数据表明lncRNA CASC9的表达与GC的侵袭性病理特征相关,它可能作为一种潜在的癌基因来调节GC细胞的增殖、侵袭和化疗耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38c1/5362493/deb68709c562/oncotarget-08-15393-g001.jpg

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