Long non-coding RNA SOS1-IT1 promotes endometrial cancer progression by regulating hypoxia signaling pathway

Hongyang Liu; Junhu Wan; Quanling Feng; Jingyu Li; Jun Liu; Shihong Cui

doi:10.1007/s12079-021-00651-1

Long non-coding RNA SOS1-IT1 promotes endometrial cancer progression by regulating hypoxia signaling pathway

J Cell Commun Signal. 2022 Jun;16(2):253-270. doi: 10.1007/s12079-021-00651-1. Epub 2021 Oct 12.

Authors

Hongyang Liu^#¹, Junhu Wan^#², Quanling Feng², Jingyu Li³, Jun Liu⁴, Shihong Cui⁵

Affiliations

¹ Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
² Department of Clinical Laboratory, Key Clinical Laboratory of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
³ Department of Neurology, Yuzhou People's Hospital, Yuzhou, 461670, Henan, China.
⁴ Department of General Surgery, Shangqiu Medical College, Zhecheng People's Hospital, Shangqiu, 476000, Henan, China.
⁵ Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. cuishzzuedu@163.com.

^# Contributed equally.

Abstract

Endometrial cancer (EC) is one of the most common types of gynecological cancer. Hypoxia is an important clinical feature and regulates various tumor processes. However, the prognostic value of hypoxia-related lncRNA in EC remains to be further elucidated. Here, we aimed to characterize the molecular features of EC by the development of a classification system based on the expression profile of hypoxia-related lncRNA. Based on univariate Cox regression analysis, we identified 17 hypoxia-related lncRNAs significantly associated with overall survival. Next, the least absolute shrinkage and selection operator Cox regression model was utilized to construct a multigene signature in the TCGA EC cohort. The risk score was confirmed as an independent predictor for overall survival in multivariate Cox regression analysis and receiver operating characteristic (ROC) curve analysis. Besides, the survival time of EC patients in different risk group was significantly correlated to clinicopathologic factors, such as age, stage and grade. Furthermore, hypoxia-related lncRNA associated with the high-risk group were involved in various aspects of the malignant progression of EC via Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and Gene Set Enrichment Analysis. Moreover, the risk score was closely correlated to immunotherapy response, microsatellite instability and tumor mutation burden. Finally, we select one hypoxia-related lncRNA SOS1-IT1 to validate its role in hypoxia and EC progression. Interestingly, we found SOS1-IT1 was overexpressed in tumor tissues, and closely correlated with clinicopathological parameters of EC. The expression level of SOS1-IT1 was significantly increased under hypoxia condition. Additionally, the important hypoxia regulatory factor HIF-1α can directly bind SOS1-IT1 promoter region, and affect its expression level. In summary, this study established a new EC classification based on the hypoxia-related lncRNA signature, thereby provide a novel sight to understand the potential mechanism of human EC development.

Keywords: Endometrial cancer; Hypoxia; Prognostic prediction; SOS1-IT1; lncRNA.