A systematic survey of LU domain-containing proteins reveals a novel human gene, LY6A, which encodes the candidate ortholog of mouse Ly-6A/Sca-1 and is aberrantly expressed in pituitary tumors.
10.1007/s11684-022-0968-4
- Author:
Dan LIU
1
;
Chunhui XU
2
;
Yanting LIU
3
;
Wen OUYANG
1
;
Shaojian LIN
3
;
Aining XU
1
;
Yuanliang ZHANG
1
;
Yinyin XIE
1
;
Qiuhua HUANG
1
;
Weili ZHAO
1
;
Zhu CHEN
1
;
Lan WANG
2
;
Saijuan CHEN
4
;
Jinyan HUANG
5
;
Zhe Bao WU
6
;
Xiaojian SUN
7
Author Information
1. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
2. CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
3. Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
4. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. sjchen@stn.sh.cn.
5. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. huangjinyan@zju.edu.cn.
6. Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. zhebaowu@aliyun.com.
7. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. xjsun@sibs.ac.cn.
- Publication Type:Journal Article
- Keywords:
GPI-anchored protein;
LU domain-containing protein family;
LY6A;
biomarker;
nonsynonymous SNP;
novel human gene;
pituitary tumor
- MeSH:
Humans;
Membrane Proteins/genetics*;
Pituitary Neoplasms/genetics*;
Biomarkers
- From:
Frontiers of Medicine
2023;17(3):458-475
- CountryChina
- Language:English
-
Abstract:
The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.
