LINC00261 Inhibits Esophageal Cancer Radioresistance by Down-Regulating microRNA-552-3p and Promoting DIRAS1

Baolong Yang, Hongbing Ma, Yan Bian Department of Radiotherapy Oncology, The Second Affiliated Hospital of Xi ‘an Jiaotong University, Xi ‘an, Shanxi Province, 710004, People’s Republic of ChinaCorrespondence: Hongbing Ma; Yan BianDepartment of Radiotherapy Oncology, The Second Affiliated Hospital of Xi ‘an Jiaotong University, Xiwu Road No. 157, Xi ‘an, Shanxi Province, 710004, People’s Republic of ChinaTel +86-13991845066Email mahongbing0530@163.com; mcgddaxxnaand0xkx@163.comObjective: 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.Methods: 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.Results: 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.Conclusion: 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.Keywords: esophageal cancer, radioresistance, long intergenic non-protein coding RNA 00261, microRNA-552-3p, DIRAS1, TE-1-R