Annotation and cluster analysis of long noncoding RNA linked to male sex and estrogen in cancers

Shouping Liu; Weiwei Lai; Ying Shi; Na Liu; Lianlian Ouyang; Ziying Zhang; Ling Chen; Xiang Wang; Banglun Qian; Desheng Xiao; Qin Yan; Ya Cao; Shuang Liu; Yongguang Tao

doi:10.1038/s41698-020-0110-5

Annotation and cluster analysis of long noncoding RNA linked to male sex and estrogen in cancers

NPJ Precis Oncol. 2020 Mar 3:4:5. doi: 10.1038/s41698-020-0110-5. eCollection 2020.

Authors

Shouping Liu^{1

2}, Weiwei Lai^{1

2}, Ying Shi^{1

2}, Na Liu^{1

2}, Lianlian Ouyang^{1

2}, Ziying Zhang^{1

2}, Ling Chen^{1

2}, Xiang Wang³, Banglun Qian³, Desheng Xiao^{1

4

5}, Qin Yan⁶, Ya Cao¹, Shuang Liu^{1

4}, Yongguang Tao^{1

2

3}

Affiliations

¹ 1Department of Pathology, Xiangya Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education) and School of Basic Medicine, Central South University, 410078 Hunan, China.
² 2NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute, Central South University, 410078 Changsha, Hunan China.
³ 3Department of Thoracic Surgery, Hunan Key Laboratory of Early Diagnosis and Precision Therapy in Lung Cancer, Second Xiangya Hospital, Central South University, 410011 Changsha, China.
⁴ 4Department of Oncology, Institute of Medical Sciences, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 410008 Changsha, Hunan China.
⁵ 5Department of Pathology, School of Basic Medicine and Xiangya Hospital, Central South University, 410008 Changsha, Hunan China.
⁶ 6Department of Pathology, Yale School of Medicine, New Haven, CT 06520 USA.

Abstract

The sex difference in cancer occurrence is a consistent finding in cancer epidemiology. Several solid tumors, including lung cancer, colorectal cancer, hepatic carcinoma, and renal carcinoma, are generally more common in males. Although sexual dimorphism is attributed to hormonal or behavioral differences, evidence for the function of lncRNA is lacking in sex-specific cancers. We show here that LINC00263 is one of the most dysregulated lncRNAs in lung adenocarcinomas and is upregulated in lung adenocarcinoma, colorectal cancer, and renal carcinoma, especially in male patients compared to females. LINC00263 functions as an oncogene by promoting translocation of p65 into the nucleus to activate the NF-κB-signaling pathway through interaction with IKKα in the cytoplasm. The expression of LINC00263 is strongly correlated with ESR1, and it is decreased after treatment with estrogen. Ligand-activated ER could inhibit the function of LINC00263 by inhibiting NF-κB from cytoplasmic translocation into the nucleus. The inhibitory effect of estrogen on LINC00263 indicates its differential expression in male and female patients. Our findings indicate that LINC00263 is linked to male sex and estrogen as an oncogene, and these findings might help in the exploration of the mechanisms of differential gene regulation in sex-specific cancers.

Keywords: Cancer genomics; Computational biology and bioinformatics.