TH1L Involvement in Colorectal Cancer Pathogenesis by Regulation of CCL20 Through the NF-κB Signalling Pathway

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2024 May 29

PMID 38809918

Authors

Shaochang Wang

Yujing Sun

Chunya Li

Yueyang Chong

Meihong Ai

Yanxia Wang

Haiyun Shi

Yu Shang

Affiliations

Soon will be listed here.

Abstract

TH1L (also known as NELF-C/D) is a member of the Negative Elongation Factor (NELF) complex, which is a metazoan-specific factor that regulates RNA Polymerase II (RNAPII) pausing and transcription elongation. However, the function and molecular mechanisms of TH1L in cancer progression are still largely unknown. In this study, we found that TH1L was highly expressed in colorectal cancer (CRC) tissues and the faeces of CRC patients. Overexpression of TH1L significantly enhanced the proliferation and migration of CRC cells, while its knockdown markedly suppressed these processes. In mechanism, RNA sequencing revealed that CCL20 was upregulated in TH1L-overexpressed CRC cells, leading to activation of the NF-κB signalling pathway. Rescue assays showed that knockdown of CCL20 could impair the tumour-promoting effects of THIL in CRC cells. Taken together, these results suggest that TH1L may play a vital role via the CCL20/NF-κB signalling pathway in CRC proliferation and migration and may serve as a potential target for diagnosis and therapy of CRC.

Citing Articles

TH1L involvement in colorectal cancer pathogenesis by regulation of CCL20 through the NF-κB signalling pathway.

Wang S, Sun Y, Li C, Chong Y, Ai M, Wang Y J Cell Mol Med. 2024; 28(10):e18391.

PMID: 38809918 PMC: 11135906. DOI: 10.1111/jcmm.18391.

References

Zhai R, Xu F, Zhang P, Zhang W, Wang H, Wang J . The Diagnostic Performance of Stool DNA Testing for Colorectal Cancer: A Systematic Review and Meta-Analysis. Medicine (Baltimore). 2016; 95(5):e2129. PMC: 4748866. DOI: 10.1097/MD.0000000000002129. View

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

Kobayashi Y, Masuda T, Fujii A, Shimizu D, Sato K, Kitagawa A . Mitotic checkpoint regulator RAE1 promotes tumor growth in colorectal cancer. Cancer Sci. 2021; 112(8):3173-3189. PMC: 8353924. DOI: 10.1111/cas.14969. View

Postma C, Terwischa S, Hermsen M, van der Sijp J, Meijer G . Gain of chromosome 20q is an indicator of poor prognosis in colorectal cancer. Cell Oncol. 2007; 29(1):73-5. PMC: 4617993. DOI: 10.1155/2007/137592. View

Cheng X, Li Y, Tan J, Sun B, Xiao Y, Fang X . CCL20 and CXCL8 synergize to promote progression and poor survival outcome in patients with colorectal cancer by collaborative induction of the epithelial-mesenchymal transition. Cancer Lett. 2014; 348(1-2):77-87. DOI: 10.1016/j.canlet.2014.03.008. View

Arnold M, Sierra M, Laversanne M, Soerjomataram I, Jemal A, Bray F . Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2016; 66(4):683-691. DOI: 10.1136/gutjnl-2015-310912. View

Yang Y, Zou W, Kong X, Wang H, Zong H, Jiang J . Trihydrophobin 1 attenuates androgen signal transduction through promoting androgen receptor degradation. J Cell Biochem. 2010; 109(5):1013-24. DOI: 10.1002/jcb.22484. View

Carvalho B, Postma C, Mongera S, Hopmans E, Diskin S, van de Wiel M . Multiple putative oncogenes at the chromosome 20q amplicon contribute to colorectal adenoma to carcinoma progression. Gut. 2008; 58(1):79-89. DOI: 10.1136/gut.2007.143065. View

Narita T, Yamaguchi Y, Yano K, Sugimoto S, Chanarat S, Wada T . Human transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex. Mol Cell Biol. 2003; 23(6):1863-73. PMC: 149481. DOI: 10.1128/MCB.23.6.1863-1873.2003. View

10.

Nagarsheth N, Wicha M, Zou W . Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat Rev Immunol. 2017; 17(9):559-572. PMC: 5731833. DOI: 10.1038/nri.2017.49. View

11.

Loo L, Tiirikainen M, Cheng I, Lum-Jones A, Seifried A, Church J . Integrated analysis of genome-wide copy number alterations and gene expression in microsatellite stable, CpG island methylator phenotype-negative colon cancer. Genes Chromosomes Cancer. 2013; 52(5):450-66. PMC: 4019504. DOI: 10.1002/gcc.22043. View

12.

Yuan Z, Liang X, Zhan Y, Wang Z, Xu J, Qiu Y . Targeting CD133 reverses drug-resistance via the AKT/NF-κB/MDR1 pathway in colorectal cancer. Br J Cancer. 2020; 122(9):1342-1353. PMC: 7188877. DOI: 10.1038/s41416-020-0783-0. View

13.

Soleimani A, Rahmani F, Ferns G, Ryzhikov M, Avan A, Hassanian S . Role of the NF-κB signaling pathway in the pathogenesis of colorectal cancer. Gene. 2019; 726:144132. DOI: 10.1016/j.gene.2019.144132. View

14.

Ahlquist D, Sargent D, Loprinzi C, Levin T, Rex D, Ahnen D . Stool DNA and occult blood testing for screen detection of colorectal neoplasia. Ann Intern Med. 2008; 149(7):441-50, W81. PMC: 4016975. DOI: 10.7326/0003-4819-149-7-200810070-00004. View

15.

Xia Y, Shen S, Verma I . NF-κB, an active player in human cancers. Cancer Immunol Res. 2014; 2(9):823-30. PMC: 4155602. DOI: 10.1158/2326-6066.CIR-14-0112. View

16.

Muller M, Ibrahim A, Arends M . Molecular pathological classification of colorectal cancer. Virchows Arch. 2016; 469(2):125-34. PMC: 4978761. DOI: 10.1007/s00428-016-1956-3. View

17.

Voutsadakis I . Chromosome 20q11.21 Amplifications in Colorectal Cancer. Cancer Genomics Proteomics. 2021; 18(3 Suppl):487-496. PMC: 8240038. DOI: 10.21873/cgp.20274. View

18.

Yang H, Xia B, Jiang B, Wang G, Yang Y, Chen H . Diagnostic value of stool DNA testing for multiple markers of colorectal cancer and advanced adenoma: a meta-analysis. Can J Gastroenterol. 2013; 27(8):467-75. PMC: 3956036. DOI: 10.1155/2013/258030. View

19.

Hari K, Santerre A, Sekelsky J, McKim K, Boyd J, Hawley R . The mei-41 gene of D. melanogaster is a structural and functional homolog of the human ataxia telangiectasia gene. Cell. 1995; 82(5):815-21. DOI: 10.1016/0092-8674(95)90478-6. View

20.

Wang S, Sun Y, Li C, Chong Y, Ai M, Wang Y . TH1L involvement in colorectal cancer pathogenesis by regulation of CCL20 through the NF-κB signalling pathway. J Cell Mol Med. 2024; 28(10):e18391. PMC: 11135906. DOI: 10.1111/jcmm.18391. View