ELOA promotes tumor growth and metastasis by activating RBP1 in gastric cancer

被引:0
作者
Tian, Lu [1 ,2 ]
Gong, Liang [1 ,2 ,3 ]
Hao, Chu [1 ,2 ]
Feng, Yuyang [1 ,2 ]
Yao, Surui [1 ,2 ]
Fei, Bojian [4 ]
Wang, Xue [1 ,2 ,5 ]
Huang, Zhaohui [1 ,2 ,6 ]
机构
[1] Jiangnan Univ, Wuxi Sch Med, Lab Canc Epigenet, Wuxi, Peoples R China
[2] Jiangnan Univ, Wuxi Canc Inst, Affiliated Hosp, Wuxi, Peoples R China
[3] Jiangnan Univ, Sch Biotechnol, Key Lab Carbohydrate Chem & Biotechnol, Minist Educ, Wuxi, Peoples R China
[4] Jiangnan Univ, Dept Gastrointestinal Surg, Affiliated Hosp, Wuxi, Peoples R China
[5] Jiangnan Univ, Wuxi Sch Med, Lab Canc Epigenet, Wuxi 214122, Peoples R China
[6] Jiangnan Univ, Wuxi Canc Inst, Affiliated Hosp, Wuxi 214062, Peoples R China
来源
CANCER MEDICINE | 2023年 / 12卷 / 18期
基金
中国国家自然科学基金;
关键词
elongin A; gastric cancer; metastasis; miR-490-3p; RBP1; transcription; RETINOL-BINDING-PROTEIN; INHIBITS CELL-PROLIFERATION; ELONGATION; EXPRESSION; ELONGIN;
D O I
10.1002/cam4.6516
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Elongin A (ELOA), our previous work revealed, serves as a novel tumor suppressor in colorectal cancer. However, the function and mechanism of ELOA in other cancer types, including gastric cancer (GC), remain to be elucidated.Methods The expression of ELOA was measured by quantitative reverse transcription-polymerase chain reaction and western blot. The effects of ELOA on GC growth and metastasis were assessed through a series of in-vitro and in-vivo assays. Furthermore, the potential mechanism of ELOA was revealed by RNA sequencing, dual luciferase reporter assay, chromatin immunoprecipitation, and rescue experiments in GC.Results We uncovered increased expression of ELOA in GC tissues compared with paired normal tissues via bioinformatic analyses and our sample detection. Enhanced ELOA expression in GC tissues was obviously correlated with poor tumor differentiation, lymph node metastasis, advanced tumor stage, and a poor prognosis. A series of functional experiments showed that ELOA promoted the proliferation and metastasis of GC. Mechanistically, we revealed that the decreased levels of miR-490-3p caused the upregulation of ELOA in GC. Both RNA-seq and ChIP assays revealed that ELOA transcriptionally activated retinol-binding protein 1 (RBP1) by binding to its promotor. Furthermore, specific knockdown of RBP1 reduced the tumor-promoting ability of ELOA in GC cells.Conclusions In summary, our findings demonstrate that ELOA exerts oncogenic properties by activating RBP1 expression, providing the basis for a promising therapeutic target in GC.
引用
收藏
页码:18946 / 18959
页数:14
相关论文
共 41 条
[1]   Elongin A associates with actively transcribed genes and modulates enhancer RNA levels with limited impact on transcription elongation rate in vivo [J].
Ardehali, M. Behfar ;
Damle, Manashree ;
Perea-Resa, Carlos ;
Blower, Michael D. ;
Kingston, Robert E. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2021, 296
[2]   The inducible elongin A elongation activation domain: Structure, function and interaction with the elongin BC complex [J].
Aso, T ;
Haque, D ;
Barstead, RJ ;
Conaway, RC ;
Conaway, JW .
EMBO JOURNAL, 1996, 15 (20) :5557-5566
[3]   ELONGIN (SIII) - A MULTISUBUNIT REGULATOR OF ELONGATION BY RNA-POLYMERASE-II [J].
ASO, T ;
LANE, WS ;
CONAWAY, JW ;
CONAWAY, RC .
SCIENCE, 1995, 269 (5229) :1439-1443
[4]   Holo-Retinol-Binding Protein and Its Receptor STRA6 Drive Oncogenic Transformation [J].
Berry, Daniel C. ;
Levi, Liraz ;
Noy, Noa .
CANCER RESEARCH, 2014, 74 (21) :6341-6351
[5]   SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop [J].
Bian, Zehua ;
Zhou, Mingyue ;
Cui, Kaisa ;
Yang, Fan ;
Cao, Yulin ;
Sun, Shengbai ;
Liu, Bingxin ;
Gong, Liang ;
Li, Jiuming ;
Wang, Xue ;
Li, Chaoqun ;
Yao, Surui ;
Yin, Yuan ;
Huang, Shenglin ;
Fei, Bojian ;
Huang, Zhaohui .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2021, 40 (01)
[6]   Aberrant Expression of Retinoic Acid Signaling Molecules Influences Patient Survival in Astrocytic Gliomas [J].
Campos, Benito ;
Centner, Franz-Simon ;
Bermejo, Justo Lorenzo ;
Ali, Ramadan ;
Dorsch, Katharina ;
Wan, Feng ;
Felsberg, Joerg ;
Ahmadi, Rezvan ;
Grabe, Niels ;
Reifenberger, Guido ;
Unterberg, Andreas ;
Burhenne, Juergen ;
Herold-Mende, Christel .
AMERICAN JOURNAL OF PATHOLOGY, 2011, 178 (05) :1953-1964
[7]   EXOSC8 promotes colorectal cancer tumorigenesis via regulating ribosome biogenesis-related processes [J].
Cui, Kaisa ;
Gong, Liang ;
Zhang, Han ;
Chen, Ying ;
Liu, Bingxin ;
Gong, Zhicheng ;
Li, Jiuming ;
Wang, Yuanben ;
Sun, Shengbai ;
Li, Yajun ;
Zhang, Qiang ;
Cao, Yulin ;
Li, Qilin ;
Fei, Bojian ;
Huang, Zhaohui .
ONCOGENE, 2022, 41 (50) :5397-5410
[8]   A novel high-risk subpopulation identified by CTSL and ZBTB7B in gastric cancer [J].
Cui, Kaisa ;
Yao, Surui ;
Liu, Bingxin ;
Sun, Shengbai ;
Gong, Liang ;
Li, Qilin ;
Fei, Bojian ;
Huang, Zhaohui .
BRITISH JOURNAL OF CANCER, 2022, 127 (08) :1450-1460
[9]   Comprehensive characterization of the rRNA metabolism-related genes in human cancer [J].
Cui, Kaisa ;
Liu, Cheng ;
Li, Xu ;
Zhang, Qiang ;
Li, Youjun .
ONCOGENE, 2020, 39 (04) :786-800
[10]   STAT3-mediated upregulation of the AIM2 DNA sensor links innate immunity with cell migration to promote epithelial tumourigenesis [J].
Dawson, Ruby E. ;
Deswaerte, Virginie ;
West, Alison C. ;
Tang, Ke ;
West, Alice J. ;
Balic, Jesse J. ;
Gearing, Linden J. ;
Saad, Mohamed, I ;
Yu, Liang ;
Wu, Yonghui ;
Bhathal, Prithi S. ;
Kumar, Beena ;
Chakrabarti, Jayati T. ;
Zavros, Yana ;
Oshima, Hiroko ;
Klinman, Dennis M. ;
Oshima, Masanobu ;
Tan, Patrick ;
Jenkins, Brendan J. .
GUT, 2022, 71 (08) :1515-1531