Integrating apaQTL and eQTL analysis identifies a potential causal variant associated with lung adenocarcinoma risk in the Chinese population

被引：1

作者：

Xu, Huiwen ^{[1
]}

Wu, Yutong ^{[1
]}

Chen, Qiong ^{[1
]}

Yu, Yuhui ^{[2
,3
]}

Meng, Qianyao ^{[4
]}

Qin, Na ^{[2
,3
]}

Zhang, Wendi ^{[1
]}

Tao, Xiaobo ^{[1
]}

Li, Siqi ^{[1
]}

Tian, Tian ^{[1
]}

Zhang, Lei ^{[1
]}

Ma, Hongxia ^{[2
,3
]}

Cui, Jiahua ^{[1
]}

Chu, Minjie ^{[1
]}

机构：

[1] Nantong Univ, Sch Publ Hlth, Dept Epidemiol, Nantong, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Dept Epidemiol, Nanjing, Jiangsu, Peoples R China

[3] Nanjing Med Univ, Collaborat Innovat Ctr Canc Personalized Med, Jiangsu Key Lab Canc Biomarkers Prevent & Treatmen, Nanjing, Jiangsu, Peoples R China

[4] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA USA

来源：

COMMUNICATIONS BIOLOGY | 2024年 / 7卷 / 01期

基金：

中国国家自然科学基金;

关键词：

ALTERNATIVE POLYADENYLATION; CANCER;

D O I：

10.1038/s42003-024-06502-0

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Alternative polyadenylation (APA) plays a crucial role in cancer biology. Here, we used data from the 3 ' aQTL-atlas, GTEx, and the China Nanjing Lung Cancer GWAS database to explore the association between apaQTL/eQTL-SNPs and the risk of lung adenocarcinoma (LUAD). The variant T allele of rs277646 in NIT2 is associated with an increased risk of LUAD (OR = 1.12, P = 0.015), lower PDUI values, and higher NIT2 expression. The 3 ' RACE experiment showed multiple poly (A) sites in NIT2, with the rs277646-T allele causing preferential use of the proximal poly (A) site, resulting in a shorter 3 ' UTR transcript. This leads to the loss of the hsa-miR-650 binding site, thereby affecting LUAD malignant phenotypes by regulating the expression level of NIT2. Our findings may provide new insights into understanding and exploring APA events in LUAD carcinogenesis. The authors explore alternative polyadenylation (APA) related genes in lung adenocarcinoma(LUAD). By integrating APA-related LUAD genes, 3 ' aQTL-atlas and eQTL analysis, they identify 28 candidate LUAD-related apaQTL/eQTL-SNPs.

引用

页数：13

共 27 条

[1] The GTEx Consortium atlas of genetic regulatory effects across human tissues [J].

Aguet, Francois ;

Barbeira, Alvaro N. ;

Bonazzola, Rodrigo ;

Brown, Andrew ;

Castel, Stephane E. ;

Jo, Brian ;

Kasela, Silva ;

Kim-Hellmuth, Sarah ;

Liang, Yanyu ;

Parsana, Princy ;

Flynn, Elise ;

Fresard, Laure ;

Gamazon, Eric R. ;

Hamel, Andrew R. ;

He, Yuan ;

Hormozdiari, Farhad ;

Mohammadi, Pejman ;

Munoz-Aguirre, Manuel ;

Ardlie, Kristin G. ;

Battle, Alexis ;

Bonazzola, Rodrigo ;

Brown, Christopher D. ;

Cox, Nancy ;

Dermitzakis, Emmanouil T. ;

Engelhardt, Barbara E. ;

Garrido-Martin, Diego ;

Gay, Nicole R. ;

Getz, Gad ;

Guigo, Roderic ;

Hamel, Andrew R. ;

Handsaker, Robert E. ;

He, Yuan ;

Hoffman, Paul J. ;

Hormozdiari, Farhad ;

Im, Hae Kyung ;

Jo, Brian ;

Kasela, Silva ;

Kashin, Seva ;

Kim-Hellmuth, Sarah ;

Kwong, Alan ;

Lappalainen, Tuuli ;

Li, Xiao ;

Liang, Yanyu ;

MacArthur, Daniel G. ;

Mohammadi, Pejman ;

Montgomery, Stephen B. ;

Munoz-Aguirre, Manuel ;

Rouhana, John M. ;

Hormozdiari, Farhad ;

Im, Hae Kyung .

SCIENCE, 2020, 369 (6509) :1318-1330

[2] A Decade of GWAS Results in Lung Cancer [J].

Bosse, Yohan ;

Amos, Christopher I. .

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2018, 27 (04) :363-379

[3] Indoor Air Pollution Increases the Risk of Lung Cancer [J].

Chen, Ke-Cheng ;

Tsai, Shih-Wei ;

Shie, Ruei-Hao ;

Zeng, Chian ;

Yang, Hsiao-Yu .

INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH, 2022, 19 (03)

[4] NIT2 overexpression predicts poor prognosis in tongue squamous cell carcinoma patients [J].

Chen, Shan ;

Wang, Zengyan ;

Feng, Chongjin .

MOLECULAR BIOLOGY REPORTS, 2020, 47 (03) :1553-1561

[5] Identification of macrophage related gene in colorectal cancer patients and their functional roles [J].

Chen, Yingxiang ;

Zhang, Cui ;

Zou, Xiang ;

Yu, Miao ;

Yang, Bo ;

Ji, Chen-Feng ;

Gao, Shi-Yong ;

Li, Jun ;

Liu, Bin .

BMC MEDICAL GENOMICS, 2021, 14 (01)

[6] 3′aQTL-atlas: an atlas of 3′UTR alternative polyadenylation quantitative trait loci across human normal tissues [J].

Cui, Ya ;

Peng, Fanglue ;

Wang, Dan ;

Li, Yumei ;

Li, Jason Sheng ;

Li, Lei ;

Li, Wei .

NUCLEIC ACIDS RESEARCH, 2022, 50 (D1) :D39-D45

[7] Identification of risk loci and a polygenic risk score for lung cancer: a large-scale prospective cohort study in Chinese populations [J].

Dai, Juncheng ;

Zhu, Meng ;

Wang, Yuzhuo ;

Qin, Na ;

Ma, Hongxia ;

He, Yong-Qiao ;

Zhang, Ruoxin ;

Tan, Wen ;

Fan, Jingyi ;

Wang, Tianpei ;

Zheng, Hong ;

Sun, Qi ;

Wang, Lijuan ;

Huang, Mingtao ;

Ge, Zijun ;

Yu, Canqing ;

Guo, Yu ;

Wang, Tong-Min ;

Wang, Jie ;

Xu, Lin ;

Wu, Weibing ;

Chen, Liang ;

Bian, Zheng ;

Walters, Robin ;

Millwood, Iona Y. ;

Li, Xi-Zhao ;

Wang, Xin ;

Hung, Rayjean J. ;

Christiani, David C. ;

Chen, Haiquan ;

Wang, Mengyun ;

Wang, Cheng ;

Jiang, Yue ;

Chen, Kexin ;

Chen, Zhengming ;

Jin, Guangfu ;

Wu, Tangchun ;

Lin, Dongxin ;

Hu, Zhibin ;

Amos, Christopher I. ;

Wu, Chen ;

Wei, Qingyi ;

Jia, Wei-Hua ;

Li, Liming ;

Shen, Hongbing .

LANCET RESPIRATORY MEDICINE, 2019, 7 (10) :881-891

[8] TC3A: The Cancer 3′ UTR Atlas [J].

Feng, Xin ;

Li, Lei ;

Wagner, Eric J. ;

Li, Wei .

NUCLEIC ACIDS RESEARCH, 2018, 46 (D1) :D1027-D1030

[9] Differential expression of lung adenocarcinoma transcriptome with signature of tobacco exposure [J].

Hammouz, Raneem Y. ;

Kostanek, Joanna K. ;

Dudzisz, Aleksandra ;

Witas, Piotr ;

Orzechowska, Magdalena ;

Bednarek, Andrzej K. .

JOURNAL OF APPLIED GENETICS, 2020, 61 (03) :421-437

[10] Analysis of the clinicopathological characteristics and their trends among patients with lung cancer undergoing surgery in a tertiary cancer hospital of north China during 2000-2013 [J].

Ji, Xinqiang ;

Fang, Yun ;

Liu, Jing .

JOURNAL OF THORACIC DISEASE, 2018, 10 (07) :3973-3982

← 1 2 3 →