Department of Liver and Stomach Diseases, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China.
Department of Endoscopy, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin, China.
J Gene Med. 2020 Oct;22(10):e3241. doi: 10.1002/jgm.3241. Epub 2020 Jul 27.
As one of the leading cancer-related mortalities worldwide, colorectal cancer (CRC) shows resistance to chemotherapy mainly because of drug resistance. Existing evidence has revealed that long noncoding RNAs (lncRNAs) are related to tumorigenesis and chemoresistance scenarios. However, the mechanism by which lncRNA induces chemoresistance and the postoperative prognosis of CRC both remain unclear.
The expression of a lncRNA named lncARSR in CRC tissue was tested, and its association with clinical and pathological features was analyzed. Gain-of-function and loss-of-function assays were conducted to investigate the role of lncARSR in vivo and in vitro.
Functional analysis showed that overexpressing lncARSR increased oxaliplatin (OXA) resistance of CRC cells in vitro and in vivo. Moreover, lncARSR conferred chemoresistance to CRC cells. Silencing lncARSR decreased cell viability and promoted cell apoptosis after OXA treatment, whereas overexpression of lncARSR increased cell viability and reduced cell apoptosis after OXA treatment. In addition, lncARSR overexpression induced the tumor formation capacity of colorectal cancer cells.
The results obtained in the present study show that up-regulation of lncARSR promoted OXA resistance in CRC. Our results also imply that lncARSR may be a candidate marker for CRC chemoresistance.
结直肠癌（CRC）作为全球主要的癌症相关死亡原因之一，主要由于耐药性而对化疗产生抵抗。现有证据表明，长链非编码 RNA（lncRNA）与肿瘤发生和化疗耐药情况有关。然而，lncRNA 诱导化疗耐药的机制以及 CRC 的术后预后仍不清楚。
检测 CRC 组织中 lncARSR 的表达，并分析其与临床病理特征的关系。进行功能获得和功能丧失实验，以研究 lncARSR 在体内和体外的作用。
功能分析表明，lncARSR 的过表达增加了 CRC 细胞在体外和体内对奥沙利铂（OXA）的耐药性。此外，lncARSR 赋予 CRC 细胞化疗耐药性。沉默 lncARSR 降低了 OXA 处理后的细胞活力并促进了细胞凋亡，而 lncARSR 的过表达则增加了 OXA 处理后的细胞活力并减少了细胞凋亡。此外，lncARSR 的过表达诱导了结直肠癌细胞的肿瘤形成能力。
本研究结果表明，lncARSR 的上调促进了 CRC 对 OXA 的耐药性。我们的结果还表明，lncARSR 可能是 CRC 化疗耐药的候选标志物。
