长链非编码 RNA Opa 相互作用蛋白 5 反义 RNA1 对结肠癌细胞奥沙利铂耐药性的影响及其对 microRNA-137 的调控。
Effects of long non-coding RNA Opa-interacting protein 5 antisense RNA 1 on colon cancer cell resistance to oxaliplatin and its regulation of microRNA-137.
机构信息
Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130000, Jilin Province, China.
Department of Hepatopancreatobiliary Surgery, China-Japan Union Hospital of Jilin University, Changchun 130000, Jilin Province, China.
出版信息
World J Gastroenterol. 2020 Apr 7;26(13):1474-1489. doi: 10.3748/wjg.v26.i13.1474.
BACKGROUND
The incidence of colon cancer (CC) is currently high, and is mainly treated with chemotherapy. Oxaliplatin (L-OHP) is a commonly used drug in chemotherapy; however, long-term use can induce drug resistance and seriously affect the prognosis of patients. Therefore, this study investigated the mechanism of Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) on L-OHP resistance by determining the expression of OIP5-AS1 and microRNA-137 (miR-137) in CC cells and the effects on L-OHP resistance, with the goal of identifying new targets for the treatment of CC.
AIM
To study the effects of long non-coding RNA OIP5-AS1 on L-OHP resistance in CC cell lines and its regulation of miR-137.
METHODS
A total of 114 CC patients admitted to China-Japan Union Hospital of Jilin University were enrolled, and the expression of miR-137 and OIP5-AS1 in tumor tissues and corresponding normal tumor-adjacent tissues was determined. The influence of OIP5-AS1 and miR-137 on the biological behavior of CC cells was evaluated. Resistance to L-OHP was induced in CC cells, and their activity was determined and evaluated using cell counting kit-8. Flow cytometry was used to analyze the apoptosis rate, Western blot to determine the levels of apoptosis-related proteins, and dual luciferase reporter assay combined with RNA-binding protein immunoprecipitation to analyze the relationship between OIP5-AS1 and miR-137.
RESULTS
OIP5-AS1 was up-regulated in CC tissues and cells, while miR-137 was down-regulated in CC tissues and cells. OIP5-AS1 was inversely correlated with miR-137 ( < 0.001). Silencing OIP5-AS1 expression significantly hindered the proliferation, invasion and migration abilities of CC cells and markedly increased the apoptosis rate. Up-regulation of miR-137 expression also suppressed these abilities in CC cells and increased the apoptosis rate. Moreover, silencing OIP5-AS1 and up-regulating miR-137 expression significantly intensified growth inhibition of drug-resistant CC cells and improved the sensitivity of CC cells to L-OHP. OIP5-AS1 targetedly inhibited miR-137 expression, and silencing OIP5-AS1 reversed the resistance of CC cells to L-OHP by promoting the expression of miR-137.
CONCLUSION
Highly expressed in CC, OIP5-AS1 can affect the biological behavior of CC cells, and can also regulate the resistance of CC cells to L-OHP by mediating miR-137 expression.
背景
结肠癌（CC）的发病率目前较高，主要采用化疗治疗。奥沙利铂（L-OHP）是化疗中常用的药物；然而，长期使用会导致耐药性，并严重影响患者的预后。因此，本研究通过测定 CC 细胞中 Opa 相互作用蛋白 5 反义 RNA 1（OIP5-AS1）和 microRNA-137（miR-137）的表达，探讨了 OIP5-AS1 对 L-OHP 耐药的作用机制，以期为 CC 的治疗寻找新的靶点。
目的
研究长链非编码 RNA OIP5-AS1 对 CC 细胞系 L-OHP 耐药性的影响及其对 miR-137 的调控作用。
方法
选取吉林大学中日联谊医院收治的 114 例 CC 患者，检测肿瘤组织及对应癌旁正常组织中 miR-137 和 OIP5-AS1 的表达，评估 OIP5-AS1 和 miR-137 对 CC 细胞生物学行为的影响。诱导 CC 细胞对 L-OHP 耐药，采用细胞计数试剂盒-8 测定细胞活力并进行评价。采用流式细胞术分析细胞凋亡率，采用 Western blot 检测凋亡相关蛋白水平，采用双荧光素酶报告基因检测与 RNA 结合蛋白免疫沉淀联合分析 OIP5-AS1 与 miR-137 的关系。
结果
CC 组织和细胞中 OIP5-AS1 呈高表达，CC 组织和细胞中 miR-137 呈低表达，且 OIP5-AS1 与 miR-137 呈负相关（<0.001）。沉默 OIP5-AS1 表达后明显抑制 CC 细胞的增殖、侵袭和迁移能力，并显著增加细胞凋亡率。上调 miR-137 表达也明显抑制 CC 细胞的这些能力，并增加细胞凋亡率。此外，沉默 OIP5-AS1 表达并上调 miR-137 表达可明显增强耐药性 CC 细胞的生长抑制作用，并提高 CC 细胞对 L-OHP 的敏感性。OIP5-AS1 靶向抑制 miR-137 的表达，沉默 OIP5-AS1 可通过促进 miR-137 的表达逆转 CC 细胞对 L-OHP 的耐药性。
结论
OIP5-AS1 在 CC 中高表达，可影响 CC 细胞的生物学行为，还可通过介导 miR-137 的表达来调节 CC 细胞对 L-OHP 的耐药性。
Zotero 插件