核糖体S6蛋白激酶4基因在多种肿瘤中的表达及其生物信息学分析

doi:10.3969/j.issn.1006-5725.2024.13.003

Abstract

Abstract:

Objective The aim of this study was to investigate whether there are differences in the expression spectrums of RSK4 in different tumor cells and to predict the possible protein subtypes and their biological characteristics. Methods RNA was extracted from glioma cells GL261， ovarian cancer cells ID8， breast cancer cells 4T1 and 168FARN， colon cancer cells mc38 and CT26， gastric cancer cells MFC and lung cancer cells LLC1. The expressions and splicing isomers of RSK4 were detected by RT?PCR. The biological characteristics and functions of RSK4 were analyzed by bioinformatics. Results RT?PCR results showed that RSK4 was expressed in GL261， 4T1， mc38， CT26， MFC and LLC1； and multiple splicing isomers were expressed in different tumor cells. Open reading frame analysis revealed RSK4 may encode at least 11 protein subtypes. Secondary structure analysis showed that these protein subtypes encoded by the splicing isomers were composed of α?helix， extended strand， β?turn and random coil， and had the same conserved domain. The results of protein interaction network enrichment analysis showed that RSK4 exerted kinase activity in the nucleus and cytoplasm mainly through the mTOR signaling pathway and long?term potentiation. Conclusions RSK4 has different expression spectrums in different tumor cells， and may produces a variety of protein isoforms with different nitrogen terminals， which can be involved in different biological processes through multiple signaling pathways.

Key words: ribosomal protein S6 kinase 4, transcripts, alternative splicing, bioinformatics, gene expression spectrum

CLC Number:

R730.2

Jianglin YANG,Yuanhong XU,Dezhong. LIAO. Expression of RSK4 gene in a variety of tumors and an analysis on the bioinformatics of this gene[J]. The Journal of Practical Medicine, 2024, 40(13): 1778-1784.

Figures/Tables 6

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References 26

1	YNTEMA H G， VAN DEN HELM B， KISSING J， et al. A novel ribosomal S6⁃kinase （RSK4； RPS6KA6） is commonly deleted in patients with complex X-linked mental retardation［J］. Genomics， 1999， 62（3）：332⁃343. doi:10.1006/geno.1999.6004 doi: 10.1006/geno.1999.6004
2	XU J， JIA Q， ZHANG Y， et al. Prominent roles of ribosomal S6 kinase 4 （RSK4） in cancer［J］. Pathol Res Pract， 2021， 219： 153374. doi:10.1016/j.prp.2021.153374 doi: 10.1016/j.prp.2021.153374
3	THAKUR A， XU H， WANG Y， et al. The role of X⁃linked genes in breast cancer［J］. Breast Cancer Res Treat， 2005， 93（2）： 135⁃ 143. doi:10.1007/s10549-005-4516-0 doi: 10.1007/s10549-005-4516-0
4	THAKUR A， RAHMAN K W， WU J， et al. Aberrant expression of X⁃linked genes RbAp46， Rsk4， and Cldn2 in breast cancer［J］. Mol Cancer Res， 2007， 5（2）： 171⁃181. doi:10.1158/1541-7786.mcr-06-0071 doi: 10.1158/1541-7786.mcr-06-0071
5	THAKUR A， BOLLIG A， WU J， et al. Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela⁃c⁃myc transgenic mice［J］. Mol Cancer， 2008， 7：11. doi:10.1186/1476-4598-7-11 doi: 10.1186/1476-4598-7-11
6	THAKUR A， SUN Y， BOLLIG A， et al. Anti⁃invasive and antimetastatic activities of ribosomal protein S6 kinase 4 in breast cancer cells［J］. Clin Cancer Res， 2008， 14（14）： 4427⁃4436. doi:10.1158/1078-0432.ccr-08-0458 doi: 10.1158/1078-0432.ccr-08-0458
7	SUN Y， CAO S， YANG M， et al. Basic anatomy and tumor biology of the RPS6KA6 gene that encodes the p90 ribosomal S6 kinase⁃4［J］. Oncogene， 2013， 32（14）： 1794⁃1810. doi:10.1038/onc.2012.200 doi: 10.1038/onc.2012.200
8	NAGUMO Y， VILLAREAL M O， ISODA H， et al. RSK4 confers paclitaxel resistance to ovarian cancer cells， which is resensitized by its inhibitor BI⁃D1870［J］. Biochem Biophys Res Commun， 2023， 679： 23⁃30. doi:10.1016/j.bbrc.2023.08.060 doi: 10.1016/j.bbrc.2023.08.060
9	PANG F， ZHANG L， LI M， et al. Ribosomal S6 protein kinase 4 promotes resistance to EZH2 inhibitors in glioblastoma［J］. Cancer Gene Ther， 2023， 30（12）： 1636⁃1648. doi:10.1038/s41417-023-00666-3 doi: 10.1038/s41417-023-00666-3
10	STEVENS M， OLTEAN S. Modulation of the Apoptosis Gene Bcl⁃x Function Through Alternative Splicing［J］. Front Genet， 2019， 10：804. doi:10.3389/fgene.2019.00804 doi: 10.3389/fgene.2019.00804
11	强晓，耿贝贝，刘四喜，等. 转录组学技术在急性白血病诊治中的应用研究进展［J］. 实用医学杂志， 2023， 39（22）： 3010⁃3014. doi:10.3969/j.issn.1006-5725.2023.22.027 doi: 10.3969/j.issn.1006-5725.2023.22.027
12	SUN Y， SRIRAMAJAYAM K， LUO D， et al. A quick， cost⁃free method of purification of DNA fragments from agarose gel［J］. J Cancer， 2012， 3： 93⁃95. doi:10.7150/jca.4163 doi: 10.7150/jca.4163
13	孙国瑞，许军鹏，罗利琼，等. 核糖体S6蛋白激酶4在恶性肿瘤中研究进展［J］. 临床军医杂志， 2021， 49（3）：356⁃357，359.
14	伍越，杨华伟. RSK4与恶性肿瘤［J］. 中国癌症防治杂志， 2017， 9（4）： 326⁃328. doi:10.3969/j.issn.1674-5671.2017.04.17 doi: 10.3969/j.issn.1674-5671.2017.04.17
15	CHRYSOSTOMOU S， ROY R， PRISCHI F， et al. Repurposed floxacins targeting RSK4 prevent chemoresistance and metastasis in lung and bladder cancer［J］. Sci Transl Med， 2021， 13（602）： eaba4627. doi:10.1126/scitranslmed.aba4627 doi: 10.1126/scitranslmed.aba4627
16	ARECHAVALETA⁃VELASCO F， DOMINGUEZ⁃LOPEZ P， ACOSTA⁃JIMENEZ E， et al. Ribosomal S6 kinase 4 （RSK4） tumor suppressor gene promoter methylation status in ovarian cancer［J］. Mol Biol Rep， 2023， 50（8）： 6863⁃6870. doi:10.1007/s11033-023-08609-9 doi: 10.1007/s11033-023-08609-9
17	CHEN S， SECKL M J， LORENTZEN M P G， et al. Differential Expression of RSK4 Transcript Isoforms in Cancer and Its Clinical Relevance［J］. Int J Mol Sci， 2022， 23（23）： 14569. doi:10.3390/ijms232314569 doi: 10.3390/ijms232314569
18	KORNBLIHTT A R， SCHOR I E， ALLÓ M， et al. Alternative splicing： a pivotal step between eukaryotic transcription and translation［J］. Nat Rev Mol Cell Biol， 2013， 14（3）： 153⁃165. doi:10.1038/nrm3525 doi: 10.1038/nrm3525
19	KHAN M R， WELLINGER R J， LAURENT B. Exploring the Alternative Splicing of Long Noncoding RNAs［J］. Trends Genet， 2021， 37（8）： 695⁃698. doi:10.1016/j.tig.2021.03.010 doi: 10.1016/j.tig.2021.03.010
20	RODRIGUEZ J M， POZO F， DOMENICO T D I， et al. An analysis of tissue⁃specific alternative splicing at the protein level［J］. PLoS Comput Biol， 2020， 16（10）： e1008287. doi:10.1371/journal.pcbi.1008287 doi: 10.1371/journal.pcbi.1008287
21	XIONG W， GAO D， LI Y， et al. Genome⁃wide profiling of chemoradiation‑induced changes in alternative splicing in colon cancer cells［J］. Oncol Rep， 2016， 36（4）： 2142⁃2150. doi:10.3892/or.2016.5022 doi: 10.3892/or.2016.5022
22	YANG C， WU Q， HUANG K， et al. Genome⁃Wide Profiling Reveals the Landscape of Prognostic Alternative Splicing Signatures in Pancreatic Ductal Adenocarcinoma［J］. Front Oncol， 2019， 9：511. doi:10.3389/fonc.2019.00511 doi: 10.3389/fonc.2019.00511
23	DANAN⁃GOTTHOLD M， GOLAN⁃GERSTL R， EISENBERG E， et al. Identification of recurrent regulated alternative splicing events across human solid tumors［J］. Nucleic Acids Res， 2015， 43（10）： 5130⁃5144. doi:10.1093/nar/gkv210 doi: 10.1093/nar/gkv210
24	ZHANG D， HU Q， LIU X， et al. Intron retention is a hallmark and spliceosome represents a therapeutic vulnerability in aggressive prostate cancer［J］. Nat Commun， 2020， 11（1）： 2089. doi:10.1038/s41467-020-15815-7 doi: 10.1038/s41467-020-15815-7
25	KELEMEN O， CONVERTINI P， ZHANG Z， et al. Function of alternative splicing［J］. Gene， 2013， 514（1）： 1⁃30. doi:10.1016/j.gene.2012.07.083 doi: 10.1016/j.gene.2012.07.083
26	SINGH A， RAJEEVAN A， GOPALAN V， et al. Broad misappropriation of developmental splicing profile by cancer in multiple organs［J］. Nat Commun， 2022， 13（1）： 7664. doi:10.1038/s41467-022-35322-1 doi: 10.1038/s41467-022-35322-1

引物名称	引物序列（5′?3′）
mRSK4-F1918	GATGCGCTATGGACAACATC
mRSK4-R2673	TCCAGGATTGGATGATGCCT
mRSK4-F543	TGAAGAACGCAGCAACGGTT
mRSK4-R1843	TGAGTGTATGCATCGCTTGC
mRSK4-F168	TTAGAAGGACACGCCACACG
mRSK4-R891	TCCACCAAGATATCCCTCTC
mRSK4-F115	GCTGCAGTTTGAAGTCTCAC
mRSK4-v7F161	TGGATGAGCACCAAGATCTC
mRSK4-v8F62	GAGCCTTGTGGCTGCTCGAG
mRSK4-R951	TACAGCTTCCCTTCAGTCTG
mRSK4-vF157	TGGGGAACCTCCATTGACGT
mRSK4-i3F	GTGATACCCAGAGCTTATGAG
mHprt1-F60	TTACCTCACTGCTTTCCGGA
mHprt1-R672	GCCTGTATCCAACACTTCGA

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Expression of RSK4 gene in a variety of tumors and an analysis on the bioinformatics of this gene

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