Yang Baolong, Ma Hongbing, Bian Yan
Department of Radiotherapy Oncology, The Second Affiliated Hospital of Xi 'an Jiaotong University, Xi 'an, Shanxi Province, 710004, People's Republic of China.
Cancer Manag Res. 2021 Nov 13;13:8559-8573. doi: 10.2147/CMAR.S332640. eCollection 2021.
Esophageal cancer (EC) represents a life-threatening tumor with an ever-increasing incidence rate. Long intergenic non-protein coding RNAs (LINCs) have also become a topic of interest in EC. In a similar light, the current study aimed to investigate the role of LINC00261 in EC radioresistance.
Firstly, radioresistant EC cell lines TE-1-R and TE-5-R were established using TE-1 and TE-5 cells. Subsequently, LINC00261, microRNA (miR)-552-3p, and DIRAS1 expression patterns in EC tissues and adjacent normal tissues and EC cells were evaluated. In addition, survival fraction (SF), colony formation, apoptosis, and γ-H2AX levels were analyzed, followed by the detection of the binding relation between LINC00261 and miR-552-3p and between miR-552-3p and DIRAS1. Lastly, xenograft transplantation was carried out to confirm the effects of LINC00261 on EC radioresistance in vivo.
LINC00261 and DIRAS1 were poorly-expressed in EC tissues and cells, but miR-552-3p was over-expressed. In EC cells with X-ray radiation, over-expression of LINC00261 reduced SF and cell viability, strengthened γ-H2AX levels, and promoted apoptosis, while all these trends were counteracted by miR-522-3p over-expression or DIRAS1 silencing. Mechanistic investigation further validated the binding relation between LINC00261 and miR-552-3p, and between miR-552-3p and DIRAS1. Moreover, LINC00261 over-expression suppressed tumor growth and reduced EC radioresistance in vivo.
Altogether, our findings indicated that LINC00261 exerts a suppressive effect on EC radioresistance via the competing endogenous RNA network to sponge miR-552-3p and up-regulate DIRAS1 transcription.
食管癌（EC）是一种发病率不断上升的危及生命的肿瘤。长链基因间非编码RNA（LINC）也已成为食管癌研究的一个热点。同样，本研究旨在探讨LINC00261在食管癌放射抗性中的作用。
首先，利用TE-1和TE-5细胞建立了放射抗性食管癌细胞系TE-1-R和TE-5-R。随后，评估了LINC00261、微小RNA（miR）-552-3p和DIRAS1在食管癌组织、癌旁正常组织及食管癌细胞中的表达模式。此外，分析了存活分数（SF）、集落形成、细胞凋亡和γ-H2AX水平，随后检测LINC00261与miR-552-3p之间以及miR-552-3p与DIRAS1之间的结合关系。最后，进行异种移植以证实LINC00261在体内对食管癌放射抗性的影响。
LINC00261和DIRAS1在食管癌组织和细胞中低表达，但miR-552-3p高表达。在接受X射线辐射的食管癌细胞中，LINC00261的过表达降低了SF和细胞活力，增强了γ-H2AX水平，并促进了细胞凋亡，而miR-522-3p的过表达或DIRAS1的沉默则抵消了所有这些趋势。机制研究进一步验证了LINC00261与miR-552-3p之间以及miR-552-3p与DIRAS1之间的结合关系。此外，LINC00261的过表达在体内抑制了肿瘤生长并降低了食管癌的放射抗性。
总之，我们的研究结果表明，LINC00261通过竞争性内源RNA网络发挥对食管癌放射抗性的抑制作用，即通过吸附miR-552-3p并上调DIRAS1转录。
