https://doi.org/10.4081/ejh.2022.3381
miR-19a targeting CLCA4 to regulate the proliferation, migration, and invasion of colorectal cancer cells
Submitted: 4 January 2022
Accepted: 19 February 2022
Published: 10 March 2022
Accepted: 19 February 2022
Abstract Views: 1475
PDF: 510
HTML: 22
HTML: 22
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
The role of miR-19a in colorectal cancer (CRC), a devastating disease with high mortality and morbidity, remains controversial. In the present study, we show that the level of miR-19a is significantly higher in clinical CRC tissue samples than in paracancerous tissue samples, and significantly higher in CRC cells lines HT29, SW480, and CaCO2 than in the normal human colon mucosal epithelial cell line NCM460. miR-19a mimics and inhibitors were synthesized and validated. Overexpression of miR-19a mimics significantly promoted, while miR-19a inhibitors inhibited, the proliferation, survival, migration, and invasion of SW480 and CaCO2 CRC cells. Furthermore, mRNA and protein levels of chloride channel accessory 4 (CLCA4) were lower in CRC cells and tissues. Bioinformatics and a luciferase reporter assay confirmed that CLCA4 was a miR-19a target. Further, miR-19a inhibition increased CLCA4 expression. The inhibitory effect of miR-19a on cell growth, survival, migration, and invasion was reversed by knockdown of CLCA4 expression. The data demonstrated that the miR-19a/CLCA4 axis modulates phospho-activation of the PI3K/AKT pathway in CRC cells. In conclusion, our results revealed that miR-19a overexpression decreases CLCA4 levels to promote CRC oncogenesis, suggesting that miR-19a inhibitors have potential applications for future therapeutic of CRC.
Downloads
Download data is not yet available.
Publication Facts
Metric
This article
Other articles
Peer reviewers
3
2.4
Reviewer profiles N/A
Author statements
Author statements
This article
Other articles
Data availability
N/A
16%
External funding
N/A
32%
Competing interests
N/A
11%
Metric
This journal
Other journals
Articles accepted
57%
33%
Days to publication
64
145
- Editor & editorial board
- profiles
- Academic society
- N/A
- Publisher
- PAGEPress Publications, Pavia, Italy
To learn about these publication facts, click 
PF is maintained by the Public Knowledge Project
Citations
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.
DOI: https://doi.org/10.3322/caac.21492
Center MM, Jemal A, Smith RA, Ward E. Worldwide variations in colorectal cancer. CA Cancer J Clin 2009;59:366-78.
DOI: https://doi.org/10.3322/caac.20038
Chen X, Qiu H, Chen Y, Wang M, Zhu P, Pan S, et al. A comparison of bevacizumab Plus TAS-102 and TAS-102 monotherapy for metastatic colorectal cancer: A systematic review and meta-analysis. Front Oncol 2021;11:690515.
DOI: https://doi.org/10.3389/fonc.2021.690515
Pratt M, Forbes JD, Knox NC, Bernstein CN, Van Domselaar G. Microbiome-mediated immune signaling in inflammatory bowel disease and colorectal cancer: support from meta-omics data. Front Cell Dev Biol 2021;9:716604.
DOI: https://doi.org/10.3389/fcell.2021.716604
Messersmith WA. NCCN guidelines updates: Management of metastatic colorectal cancer. J Natl Compr Canc Netw 2019;17:599-601.
Spartalis C, Schmidt EM, Elmasry M, Schulz GB, Kirchner T, Horst D. In vivo effects of chemotherapy on oncogenic pathways in colorectal cancer. Cancer Sci 2019;110:2529-39.
DOI: https://doi.org/10.1111/cas.14077
Torring ML, Falborg AZ, Jensen H, Neal RD, Weller D, Reguilon I, et al. Advanced-stage cancer and time to diagnosis: An International Cancer Benchmarking Partnership (ICBP) cross-sectional study. Eur J Cancer Care 2019;28:11.
DOI: https://doi.org/10.1111/ecc.13100
Piawah S, Venook AP. Targeted therapy for colorectal cancer metastases: A review of current methods of molecularly targeted therapy and the use of tumor biomarkers in the treatment of metastatic colorectal cancer. Cancer 2019;125:4139-47.
DOI: https://doi.org/10.1002/cncr.32163
Jiang M, Jin S, Han J, Li T, Shi J, Zhong Q, et al. Detection and clinical significance of circulating tumor cells in colorectal cancer. Biomark Res 2021;9:85.
DOI: https://doi.org/10.1186/s40364-021-00326-4
Grillo TG, Quaglio AEV, Beraldo RF, Lima TB, Baima JP, Di Stasi LC, et al. MicroRNA expression in inflammatory bowel disease-associated colorectal cancer. World J Gastrointest Oncol 2021;13:995-1016.
DOI: https://doi.org/10.4251/wjgo.v13.i9.995
Macias S, Michlewski G, Caceres JF. Hormonal regulation of microRNA biogenesis. Mol Cell 2009;36:172-3.
DOI: https://doi.org/10.1016/j.molcel.2009.10.006
Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 2014;15:509-24.
DOI: https://doi.org/10.1038/nrm3838
Shadbad MA, Asadzadeh Z, Derakhshani A, Hosseinkhani N, Mokhtarzadeh A, Baghbanzadeh A, et al. A scoping review on the potentiality of PD-L1-inhibiting microRNAs in treating colorectal cancer: Toward single-cell sequencing-guided biocompatible-based delivery. Biomed Pharmacother 2021;143:112213.
DOI: https://doi.org/10.1016/j.biopha.2021.112213
Pidikova P, Herichova I. miRNA clusters with up-regulated expression in colorectal cancer. Cancers (Basel) 2021;13:2979.
DOI: https://doi.org/10.3390/cancers13122979
Ghafouri-Fard S, Hussen BM, Badrlou E, Abak A, Taheri M. MicroRNAs as important contributors in the pathogenesis of colorectal cancer. Biomed Pharmacother 2021;140:111759.
DOI: https://doi.org/10.1016/j.biopha.2021.111759
He J, Wu F, Han Z, Hu M, Lin W, Li Y, et al. Biomarkers (mRNAs and non-coding RNAs) for the diagnosis and prognosis of colorectal cancer - From the body fluid to tissue level. Front Oncol 2021;11:632834.
DOI: https://doi.org/10.3389/fonc.2021.632834
Michael MZ, SM OC, van Holst Pellekaan NG, Young GP, James RJ. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 2003;1:882-91.
Pagliuca A, Valvo C, Fabrizi E, di Martino S, Biffoni M, Runci D, et al. Analysis of the combined action of miR-143 and miR-145 on oncogenic pathways in colorectal cancer cells reveals a coordinate program of gene repression. Oncogene 2013;32:4806-13.
DOI: https://doi.org/10.1038/onc.2012.495
Danielsen SA, Eide PW, Nesbakken A, Guren T, Leithe E, Lothe RA. Portrait of the PI3K/AKT pathway in colorectal cancer. Biochim Biophys Acta 2015;1855:104-21.
DOI: https://doi.org/10.1016/j.bbcan.2014.09.008
Liu Y, Liu R, Yang F, Cheng R, Chen X, Cui S, et al. miR-19a promotes colorectal cancer proliferation and migration by targeting TIA1. Mol Cancer 2017;16:53.
DOI: https://doi.org/10.1186/s12943-017-0625-8
Yin Q, Wang PP, Peng R, Zhou H. MiR-19a enhances cell proliferation, migration, and invasiveness through enhancing lymphangiogenesis by targeting thrombospondin-1 in colorectal cancer. Biochem Cell Biol 2019;97:731-9.
DOI: https://doi.org/10.1139/bcb-2018-0302
Yu FB, Sheng J, Yu JM, Liu JH, Qin XX, Mou B. MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/beta-catenin signaling pathway and affects the biological functions of colorectal cancer cells. World J Gastroenterol 2020;26:627-44.
DOI: https://doi.org/10.3748/wjg.v26.i6.627
Elble RC, Pauli BU. Tumor suppression by a proapoptotic calcium-activated chloride channel in mammary epithelium. J Biol Chem 2001;276:40510-7.
DOI: https://doi.org/10.1074/jbc.M104821200
Hou T, Zhou L, Wang L, Kazobinka G, Zhang X, Chen Z. CLCA4 inhibits bladder cancer cell proliferation, migration, and invasion by suppressing the PI3K/AKT pathway. Oncotarget 2017;8:93001-13.
DOI: https://doi.org/10.18632/oncotarget.21724
Yu Y, Walia V, Elble RC. Loss of CLCA4 promotes epithelial-to-mesenchymal transition in breast cancer cells. PLoS One 2013;8:e83943.
DOI: https://doi.org/10.1371/journal.pone.0083943
Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. Elife 2015;4:e05005.
DOI: https://doi.org/10.7554/eLife.05005
Wang X. Improving microRNA target prediction by modeling with unambiguously identified microRNA-target pairs from CLIP-ligation studies. Bioinformatics 2016;32:1316-22.
DOI: https://doi.org/10.1093/bioinformatics/btw002
Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, et al. Combinatorial microRNA target predictions. Nat Genet 2005;37:495-500.
DOI: https://doi.org/10.1038/ng1536
Liu Z, Chen M, Xie LK, Liu T, Zou ZW, Li Y, et al. CLCA4 inhibits cell proliferation and invasion of hepatocellular carcinoma by suppressing epithelial-mesenchymal transition via PI3K/AKT signaling. Aging (Albany NY) 2018;10:2570-84.
DOI: https://doi.org/10.18632/aging.101571
Zhang Y, Wang J. MicroRNAs are important regulators of drug resistance in colorectal cancer. Biol Chem 2017;398:929-38.
DOI: https://doi.org/10.1515/hsz-2016-0308
Falzone L, Lupo G, La Rosa GRM, Crimi S, Anfuso CD, Salemi R, et al. Identification of novel MicroRNAs and their diagnostic and prognostic significance in oral cancer. Cancers (Basel) 2019;11.
DOI: https://doi.org/10.3390/cancers11050610
Akshatha CR, Bhat S, Sindhu R, Shashank D, Rose Sommano S, Tapingkae W, et al. Current therapeutic options for gastric adenocarcinoma. Saudi J Biol Sci 2021;28:5371-8.
DOI: https://doi.org/10.1016/j.sjbs.2021.05.060
Li J, Liang H, Bai M, Ning T, Wang C, Fan Q, et al. miR-135b promotes cancer progression by targeting transforming growth factor beta receptor II (TGFBR2) in colorectal cancer. PLoS One 2015;10:e0130194.
DOI: https://doi.org/10.1371/journal.pone.0130194
Zhang W, Zhang T, Jin R, Zhao H, Hu J, Feng B, et al. MicroRNA-301a promotes migration and invasion by targeting TGFBR2 in human colorectal cancer. J Exp Clin Cancer Res 2014;33:113.
DOI: https://doi.org/10.1186/s13046-014-0113-6
Ma K, Pan X, Fan P, He Y, Gu J, Wang W, et al. Loss of miR-638 in vitro promotes cell invasion and a mesenchymal-like transition by influencing SOX2 expression in colorectal carcinoma cells. Mol Cancer 2014;13:118.
DOI: https://doi.org/10.1186/1476-4598-13-118
Zhang J, Fei B, Wang Q, Song M, Yin Y, Zhang B, et al. MicroRNA-638 inhibits cell proliferation, invasion and regulates cell cycle by targeting tetraspanin 1 in human colorectal carcinoma. Oncotarget 2014;5:12083-96.
DOI: https://doi.org/10.18632/oncotarget.2499
Li Z, Li Y, Wang Y. miR-19a promotes invasion and epithelial to mesenchymal transition of bladder cancer cells by targeting RhoB. J BUON 2019;24:797-804.
Peng Y, Huang D, Ma K, Deng X, Shao Z. MiR-19a as a prognostic indicator for cancer patients: a meta-analysis. Biosci Rep 2019;39:BSR20182370.
DOI: https://doi.org/10.1042/BSR20182370
Li Y, Lv S, Ning H, Li K, Zhou X, Xv H, et al. Down-regulation of CASC2 contributes to cisplatin resistance in gastric cancer by sponging miR-19a. Biomed Pharmacother 2018;108:1775-82.
DOI: https://doi.org/10.1016/j.biopha.2018.09.181
Cao X, Lai S, Hu F, Li G, Wang G, Luo X, et al. miR-19a contributes to gefitinib resistance and epithelial mesenchymal transition in non-small cell lung cancer cells by targeting c-Met. Sci Rep 2017;7:2939.
DOI: https://doi.org/10.1038/s41598-017-01153-0
Li Y, Lauriola M, Kim D, Francesconi M, D'Uva G, Shibata D, et al. Adenomatous polyposis coli (APC) regulates miR17-92 cluster through beta-catenin pathway in colorectal cancer. Oncogene 2016;35:4558-68.
DOI: https://doi.org/10.1038/onc.2015.522
Chen M, Lin M, Wang X. Overexpression of miR-19a inhibits colorectal cancer angiogenesis by suppressing KRAS expression. Oncol Rep 2018;39:619-26.
DOI: https://doi.org/10.3892/or.2017.6110
Shen P, Qu L, Wang J, Ding Q, Zhou C, Xie R, et al. LncRNA LINC00342 contributes to the growth and metastasis of colorectal cancer via targeting miR-19a-3p/NPEPL1 axis. Cancer Cell Int 2021;21:105.
DOI: https://doi.org/10.1186/s12935-020-01705-x
Patel AC, Brett TJ, Holtzman MJ. The role of CLCA proteins in inflammatory airway disease. Annu Rev Physiol 2009;71:425-49.
DOI: https://doi.org/10.1146/annurev.physiol.010908.163253
Hughes K, Blanck M, Pensa S, Watson CJ. Stat3 modulates chloride channel accessory protein expression in normal and neoplastic mammary tissue. Cell Death Dis 2016;7:e2398.
DOI: https://doi.org/10.1038/cddis.2016.302
Loewen ME, Forsyth GW. Structure and function of CLCA proteins. Physiol Rev 2005;85:1061-92.
DOI: https://doi.org/10.1152/physrev.00016.2004
Yang B, Cao L, Liu B, McCaig CD, Pu J. The transition from proliferation to differentiation in colorectal cancer is regulated by the calcium activated chloride channel A1. PLoS One 2013;8:e60861.
DOI: https://doi.org/10.1371/journal.pone.0060861
Yang B, Cao L, Liu J, Xu Y, Milne G, Chan W, et al. Low expression of chloride channel accessory 1 predicts a poor prognosis in colorectal cancer. Cancer 2015;121:1570-80.
DOI: https://doi.org/10.1002/cncr.29235
Sasaki Y, Koyama R, Maruyama R, Hirano T, Tamura M, Sugisaka J, et al. CLCA2, a target of the p53 family, negatively regulates cancer cell migration and invasion. Cancer Biol Ther 2012;13:1512-21.
DOI: https://doi.org/10.4161/cbt.22280
Walia V, Yu Y, Cao D, Sun M, McLean JR, Hollier BG, et al. Loss of breast epithelial marker hCLCA2 promotes epithelial-to-mesenchymal transition and indicates higher risk of metastasis. Oncogene 2012;31:2237-46.
DOI: https://doi.org/10.1038/onc.2011.392
Patil KS, Basak I, Pal R, Ho HP, Alves G, Chang EJ, et al. A proteomics approach to investigate miR-153-3p and miR-205-5p targets in neuroblastoma cells. PLoS One 2015;10:e0143969.
DOI: https://doi.org/10.1371/journal.pone.0143969
Skaper SD. Ion channels on microglia: therapeutic targets for neuroprotection. CNS Neurol Disord Drug Targets 2011;10:44-56.
DOI: https://doi.org/10.2174/187152711794488638
How to Cite
Li, H., & Huang, B. (2022). <em>miR-19a</em> targeting <em>CLCA4</em> to regulate the proliferation, migration, and invasion of colorectal cancer cells. European Journal of Histochemistry, 66(1). https://doi.org/10.4081/ejh.2022.3381
Copyright (c) 2022 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Antonio Franchitto, Diletta Overi, Romina Mancinelli, Anna Paola Mitterhofer, Paolo Muiesan, Francesca Tinti, Ilaria Umbro, Stefan G. Hubscher, Paolo Onori, Eugenio Gaudio, Guido Carpino, Peribiliary gland damage due to liver transplantation involves peribiliary vascular plexus and vascular endothelial growth factor , European Journal of Histochemistry: Vol. 63 No. 2 (2019)
- Enrica Cappellozza, Federico Boschi, Maddalena Sguizzato, Elisabetta Esposito, Rita Cortesi, Manuela Malatesta, Laura Calderan, A spectrofluorometric analysis to evaluate transcutaneous biodistribution of fluorescent nanoparticulate gel formulations , European Journal of Histochemistry: Vol. 66 No. 1 (2022)
You may also start an advanced similarity search for this article.
