Xiaofeng Dai1, Lihui Yu2, Xiao Chen3, Jianying Zhang4. 1. Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. xiaofeng.dai@jiangnan.edu.cn. 2. Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China. 3. School of Biotechnology, Jiangnan University, Wuxi, Jiangsu, China. 4. Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
Abstract
BACKGROUND: SNRPD1 is a spliceosome-associated protein and has previously been implicated with important roles in cancer development. METHODS: Through analyzing the differential expression patterns and clinical association of splicing associated genes among tumor and tumor adjacent samples across different tumors and among different breast cancer subtypes, we identify the tumor promotive role of SNRPD1 using multiple publicly available datasets. Through pathway, gene ontology enrichment analysis and network construction, we linked the onco-therapeutic role of SNRPD1 with cell cycle. Via a series of experimental studies including knockdown assay, qPCR, western blotting, cell cycle, drug response assay, we confirmed the higher expression of SNPRD1 at both gene and protein expression levels in triple negative breast cancer cells, as well as its roles in promoting cell cycle and chemotherapy response. RESULTS: Our study revealed that SNRPD1 over-expression was significantly associated with genes involved in cell cycle, cell mitosis and chromatin replication, and silencing SNRPD1 in breast cancer cells could lead to halted tumor cell growth and cell cycle arrest at the G0/G1 stage. We also found that triple negative breast cancer cells with reduced SNRPD1 expression lost certain sensitivity to doxorubicin whereas luminal cancer cells did not. CONCLUSIONS: Our results suggested the prognostic value of SNRPD1 on breast cancer survival, its potential as the therapeutic target halting cell cycle progression for breast cancer control, and warranted special attention on the combined use of doxorubicin and drugs targeting SNRPD1.
BACKGROUND:SNRPD1 is a spliceosome-associated protein and has previously been implicated with important roles in cancer development. METHODS: Through analyzing the differential expression patterns and clinical association of splicing associated genes among tumor and tumor adjacent samples across different tumors and among different breast cancer subtypes, we identify the tumor promotive role of SNRPD1 using multiple publicly available datasets. Through pathway, gene ontology enrichment analysis and network construction, we linked the onco-therapeutic role of SNRPD1 with cell cycle. Via a series of experimental studies including knockdown assay, qPCR, western blotting, cell cycle, drug response assay, we confirmed the higher expression of SNPRD1 at both gene and protein expression levels in triple negative breast cancer cells, as well as its roles in promoting cell cycle and chemotherapy response. RESULTS: Our study revealed that SNRPD1 over-expression was significantly associated with genes involved in cell cycle, cell mitosis and chromatin replication, and silencing SNRPD1 in breast cancer cells could lead to halted tumor cell growth and cell cycle arrest at the G0/G1 stage. We also found that triple negative breast cancer cells with reduced SNRPD1 expression lost certain sensitivity to doxorubicin whereas luminalcancer cells did not. CONCLUSIONS: Our results suggested the prognostic value of SNRPD1 on breast cancer survival, its potential as the therapeutic target halting cell cycle progression for breast cancer control, and warranted special attention on the combined use of doxorubicin and drugs targeting SNRPD1.
Entities:
Keywords:
Breast cancer; Cell cycle arrest; Prognosis; SNRPD1; Therapeutics
Authors: Lili Wang; Michael S Lawrence; Youzhong Wan; Petar Stojanov; Carrie Sougnez; Kristen Stevenson; Lillian Werner; Andrey Sivachenko; David S DeLuca; Li Zhang; Wandi Zhang; Alexander R Vartanov; Stacey M Fernandes; Natalie R Goldstein; Eric G Folco; Kristian Cibulskis; Bethany Tesar; Quinlan L Sievers; Erica Shefler; Stacey Gabriel; Nir Hacohen; Robin Reed; Matthew Meyerson; Todd R Golub; Eric S Lander; Donna Neuberg; Jennifer R Brown; Gad Getz; Catherine J Wu Journal: N Engl J Med Date: 2011-12-12 Impact factor: 91.245
Authors: Víctor Quesada; Laura Conde; Neus Villamor; Gonzalo R Ordóñez; Pedro Jares; Laia Bassaganyas; Andrew J Ramsay; Sílvia Beà; Magda Pinyol; Alejandra Martínez-Trillos; Mónica López-Guerra; Dolors Colomer; Alba Navarro; Tycho Baumann; Marta Aymerich; María Rozman; Julio Delgado; Eva Giné; Jesús M Hernández; Marcos González-Díaz; Diana A Puente; Gloria Velasco; José M P Freije; José M C Tubío; Romina Royo; Josep L Gelpí; Modesto Orozco; David G Pisano; Jorge Zamora; Miguel Vázquez; Alfonso Valencia; Heinz Himmelbauer; Mónica Bayés; Simon Heath; Marta Gut; Ivo Gut; Xavier Estivill; Armando López-Guillermo; Xose S Puente; Elías Campo; Carlos López-Otín Journal: Nat Genet Date: 2011-12-11 Impact factor: 38.330
Authors: Timothy A Graubert; Dong Shen; Li Ding; Theresa Okeyo-Owuor; Cara L Lunn; Jin Shao; Kilannin Krysiak; Christopher C Harris; Daniel C Koboldt; David E Larson; Michael D McLellan; David J Dooling; Rachel M Abbott; Robert S Fulton; Heather Schmidt; Joelle Kalicki-Veizer; Michelle O'Laughlin; Marcus Grillot; Jack Baty; Sharon Heath; John L Frater; Talat Nasim; Daniel C Link; Michael H Tomasson; Peter Westervelt; John F DiPersio; Elaine R Mardis; Timothy J Ley; Richard K Wilson; Matthew J Walter Journal: Nat Genet Date: 2011-12-11 Impact factor: 38.330
Authors: Yun Zhang; Katherine M Weh; Connor L Howard; Jean-Jack Riethoven; Jennifer L Clarke; Kiran H Lagisetty; Jules Lin; Rishindra M Reddy; Andrew C Chang; David G Beer; Laura A Kresty Journal: Mol Ther Nucleic Acids Date: 2022-08-17 Impact factor: 10.183