Qingmin Zeng1, Fuming Lei2, Yigang Chang1, Zhaoya Gao2, Yanzhao Wang2, Qingkun Gao2, Pengfei Niu2, Qiang Li3. 1. National Clinical Research Center for Cancer & Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China. 2. Department of General Surgery, Gastrointestinal Surgery, Peking University Shougang Hospital, Jin Yuan Zhuang Road No. 9, Beijing 100144, China. 3. National Clinical Research Center for Cancer & Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China. Electronic address: liqiang4016@yahoo.com.
Abstract
PURPOSE: Colorectal cancer (CRC) caused more than 65,000 mortalities worldwide per year. It is a result of one or a combination of chromosomal instability, CpG island methylator phenotype, and microsatellite instability. SNRPA1 (small nuclear ribonucleoprotein polypeptide A) is a subunit of spliceosome complex that is involved in the RNA processing. Overexpression of SNRPA1 has been implicated in a variety of cancers including CRC. Besides from its role in mediating the RNA processing, the other aspects regarding its function in the progression of colorectal cancer have not been revealed. METHODS: Herein, we combined regular gene overexpression or knock down in vitro and in vivo and microarray gene profiling analysis to decipher the unknow regulatory role of SNRPA1 in CRC. RESULTS: We found SNRPA1 widely expression in many representative CRC cell lines. Knocking down expression of SNRPA1 by shRNA lentivirus inhibited the cell proliferation in vitro and impaired tumor formation from implanted CRC cells transduced with SNRPA1 silencing shRNA lentivirus in nude mice. It also promoted the cell apoptosis by upregulating the caspase 3/7 activity. Additional microarray gene profiling analysis uncovered the gene interaction network of SNRPA1, special focus was placed on its association with tumor suppressor or oncogenes. CONCLUSIONS: According to the results of gene interaction network as well as qRT-PCR verification, it revealed that SNPRA1 regulates PIK3R1, VEGFC, MKI67, CDK1 in CRC. These novel findings identified new roles played by SNRPA1 in the progression of CRC and it may become a potential therapeutic target in the treatment of CRC.
PURPOSE:Colorectal cancer (CRC) caused more than 65,000 mortalities worldwide per year. It is a result of one or a combination of chromosomal instability, CpG island methylator phenotype, and microsatellite instability. SNRPA1 (small nuclear ribonucleoprotein polypeptide A) is a subunit of spliceosome complex that is involved in the RNA processing. Overexpression of SNRPA1 has been implicated in a variety of cancers including CRC. Besides from its role in mediating the RNA processing, the other aspects regarding its function in the progression of colorectal cancer have not been revealed. METHODS: Herein, we combined regular gene overexpression or knock down in vitro and in vivo and microarray gene profiling analysis to decipher the unknow regulatory role of SNRPA1 in CRC. RESULTS: We found SNRPA1 widely expression in many representative CRC cell lines. Knocking down expression of SNRPA1 by shRNA lentivirus inhibited the cell proliferation in vitro and impaired tumor formation from implanted CRC cells transduced with SNRPA1 silencing shRNA lentivirus in nude mice. It also promoted the cell apoptosis by upregulating the caspase 3/7 activity. Additional microarray gene profiling analysis uncovered the gene interaction network of SNRPA1, special focus was placed on its association with tumor suppressor or oncogenes. CONCLUSIONS: According to the results of gene interaction network as well as qRT-PCR verification, it revealed that SNPRA1 regulates PIK3R1, VEGFC, MKI67, CDK1 in CRC. These novel findings identified new roles played by SNRPA1 in the progression of CRC and it may become a potential therapeutic target in the treatment of CRC.