当前位置: X-MOL 学术Cell Biol. Int. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
LncRNA TTN-AS1/miR-134-5p/PAK3 axis regulates the radiosensitivity of human large intestine cancer cells through the P21 pathway and AKT/GSK-3β/β-catenin pathway.
Cell Biology International ( IF 3.3 ) Pub Date : 2020-08-04 , DOI: 10.1002/cbin.11436
Zhenkui Zuo 1 , Shuling Ji 1 , Lulu He 1 , Yage Zhang 2 , Zining Peng 2 , Jiarui Han 2
Affiliation  

Radiotherapy is an important adjuvant treatment for large intestine cancer even though it does not cause any response in many patients. The present study aimed to investigate the effects of the TTN antisense RNA 1 (TTN‐AS1) long noncoding RNA (lncRNA) on radiotherapy dynamics of large intestine cancer cells and to explore the underlying molecular mechanisms. TTN‐AS1 expression was evaluated by reverse‐transcription quantitative polymerase chain reaction, western blot, and cellular immunofluorescence, and flow cytometry analysis was used to measure apoptosis. Radiotherapy was simulated in vitro by exposing cancer cells to X‐ray. TTN‐AS1 was highly expressed in large intestine cancer cells after an X‐ray exposition for 24 hr. TTN‐AS1 knockdown improved the radiosensitivity of large intestine cancer cells and promoted apoptosis by increasing Bax/Bcl2 protein expression and the active‐caspase 3/caspase 3 ratios following X‐ray treatment. In addition, TTN‐AS1 negatively regulated miR‐134‐5p expression, and miR‐134‐5p‐mimic transfection decreased PAK3 protein expression in large intestine cancer cells. Importantly, TTN‐AS1 promoted PAK3 and P21 protein expression in HT29 cells after X‐ray treatment. Moreover, the knockdown of P21 protein expression improved radiosensitivity and promoted X‐ray‐induced apoptosis of HT29 cells. Finally, PAK3 knockdown expression decreased the p‐AKT/AKT and p‐GSK‐3β/GSK‐3β ratios and promoted the β‐catenin transfer from the nucleus to the cytoplasm. These data suggest that the TTN‐AS1 lncRNA promoted resistance to radiotherapy of large intestine cancer cells by increasing PAK3 expression via miR‐134‐5p inhibition, and this may be related to the P21 and AKT/GSK‐3β/β‐catenin pathway.

中文翻译:

LncRNA TTN-AS1 / miR-134-5p / PAK3轴通过P21途径和AKT /GSK-3β/β-catenin途径调节人大肠癌细胞的放射敏感性。

放疗是大肠癌的重要辅助治疗方法,即使它对许多患者没有任何反应。本研究旨在研究TTN反义RNA 1(TTN-AS1)长非编码RNA(lncRNA)对大肠癌细胞放射治疗动力学的影响,并探讨其潜在的分子机制。通过逆转录定量聚合酶链反应,蛋白质印迹和细胞免疫荧光评估TTN-AS1表达,并使用流式细胞仪分析测量细胞凋亡。通过将癌细胞暴露于X射线体外模拟放射疗法。X射线暴露24小时后,TTN-AS1在大肠癌细胞中高表达。TTN-AS1组合可通过提高X射线处理后Bax / Bcl2蛋白表达和active-caspase 3 / caspase 3比值来提高大肠癌细胞的放射敏感性并促进细胞凋亡。此外,TTN-AS1对miR-134-5p的表达负调控,而miR-134-5p的模拟转染降低了大肠癌细胞中PAK3的蛋白表达。重要的是,经过X射线处理后,TTN-AS1促进了HT29细胞中PAK3和P21蛋白的表达。此外,P21蛋白表达的降低可提高放射敏感性,并促进X射线诱导的HT29细胞凋亡。最后,PAK3敲低表达降低了p-AKT / AKT和p-GSK-3β/GSK-3β的比率,并促进了β-catenin从细胞核向细胞质的转移。
更新日期:2020-10-13
down
wechat
bug