Login Register Cart 0
Generic placeholder image

Current Gene Therapy

Editor-in-Chief

ISSN (Print): 1566-5232
ISSN (Online): 1875-5631

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

miRNA-1260b Promotes Breast Cancer Cell Migration and Invasion by Downregulating CCDC134

Author(s): Zhijian Huang, Shijian Zhen, Liangzi Jin, Jian Chen, Yuanyuan Han*, Wen Lei* and Fuqing Zhang*

Volume 23, Issue 1, 2023

Published on: 26 September, 2022

Page: [60 - 71] Pages: 12

DOI: 10.2174/1566523222666220901112314

Price: $65

Abstract

Background: Breast cancer (BRCA) is the most common type of cancer among women worldwide. MiR-1260b has been widely demonstrated to participate in multiple crucial biological functions of cancer tumorigenesis, but its functional effect and mechanism in human breast cancer have not been fully understood.

Methods: qRT-PCR was used to detect miR-1260b expression in 29 pairs of breast cancer tissues and normal adjacent tissues. Besides, the expression level of miR-1260b in BRCA cells was also further validated by qRT-PCR. miR-1260b played its role in the prognostic process by using Kaplan-Meier curves. In addition, miR-1260b knockdown and target gene CCDC134 overexpression model was constructed in cell line MDA-MB-231. Transwell migration and invasion assay was performed to analyze the effect of miR-1260b and CCDC134 on the biological function of BRCA cells. TargetScan and miRNAWalk were used to find possible target mRNAs. The relationship between CCDC134 and immune cell surface markers was analyzed using TIMER and database and the XIANTAO platform. GSEA analysis was used to identify possible CCDC134-associated molecular mechanisms and pathways.

Results: In the present study, miR-1260b expression was significantly upregulated in human breast cancer tissue and a panel of human breast cancer cell lines, while the secretory protein coiled-coil domain containing 134 (CCDC134) exhibited lower mRNA expression. High expression of miR-1260b was associated with poor overall survival among the patients by KM plot. Knockdown of miR-1260b significantly suppressed breast cancer cell migration and invasion and yielded the opposite result. In addition, overexpression of CCDC134 could inhibit breast cancer migration and invasion, and knockdown yielded the opposite result. There were significant positive correlations of CCDC134 with CD25 (IL2RA), CD80 and CD86. GSEA showed that miR-1260b could function through the MAPK pathway by downregulating CCDC134.

Conclusion: Collectively, these results suggested that miR-1260b might be an oncogene of breast cancer and might promote the migration and invasion of BRCA cells by down-regulating its target gene CCDC134 and activating MAPK signaling pathway as well as inhibiting immune function and causing immune escape in human breast cancer.

Keywords: Breast cancer, miR-1260b, CCDC134, MAPK signaling pathways, tumor, cancer cell.

« Previous Next »
Graphical Abstract

[1]
Erratum: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2020; 70(4): 313.
[http://dx.doi.org/10.3322/caac.21609] [PMID: 32767693]
[2]
Bianchini G, De Angelis C, Licata L, Gianni L. Treatment landscape of triple-negative breast cancer - expanded options, evolving needs. Nat Rev Clin Oncol 2022; 19(2): 91-113.
[http://dx.doi.org/10.1038/s41571-021-00565-2] [PMID: 34754128]
[3]
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71(3): 209-49.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[4]
Ruocco MR, Avagliano A, Granato G, et al. Involvement of breast cancer-associated fibroblasts in tumor development, therapy resistance and evaluation of potential therapeutic strategies. Curr Med Chem 2018; 25(29): 3414-34.
[http://dx.doi.org/10.2174/0929867325666180309120746] [PMID: 29521203]
[5]
DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin 2017; 67(6): 439-48.
[http://dx.doi.org/10.3322/caac.21412] [PMID: 28972651]
[6]
Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136(5): E359-86.
[http://dx.doi.org/10.1002/ijc.29210] [PMID: 25220842]
[7]
Jones SC, Gregory P, Nehill C, et al. Australian women’s awareness of breast cancer symptoms and responses to potential symptoms. Cancer Causes Control 2010; 21(6): 945-58.
[http://dx.doi.org/10.1007/s10552-010-9522-9] [PMID: 20177964]
[8]
Innos K, Horn-Ross PL. Risk of second primary breast cancers among women with ductal carcinoma in situ of the breast. Breast Cancer Res Treat 2008; 111(3): 531-40.
[http://dx.doi.org/10.1007/s10549-007-9807-1] [PMID: 17978879]
[9]
Li CI, Malone KE, Saltzman BS, Daling JR. Risk of invasive breast carcinoma among women diagnosed with ductal carcinoma in situ and lobular carcinoma in situ, 1988-2001. Cancer 2006; 106(10): 2104-12.
[http://dx.doi.org/10.1002/cncr.21864] [PMID: 16604564]
[10]
Zhang Y, Xiang J, Tang L, et al. Identifying breast cancer-related genes based on a novel computational framework involving KEGG pathways and PPI network modularity. Front Genet 2021; 12: 596794.
[http://dx.doi.org/10.3389/fgene.2021.596794] [PMID: 34484285]
[11]
Parkin DM, Fernández LMG. Use of statistics to assess the global burden of breast cancer. Breast J 2006; 12 (Suppl. 1): S70-80.
[http://dx.doi.org/10.1111/j.1075-122X.2006.00205.x] [PMID: 16430400]
[12]
Yang J, Ju J, Guo L, et al. Prediction of HER2-positive breast cancer recurrence and metastasis risk from histopathological images and clinical information via multimodal deep learning. Comput Struct Biotechnol J 2022; 20: 333-42.
[http://dx.doi.org/10.1016/j.csbj.2021.12.028] [PMID: 35035786]
[13]
Liu H, Qiu C, Wang B, et al. Evaluating DNA methylation, gene expression, somatic mutation, and their combinations in inferring tumor tissue-of-origin. Front Cell Dev Biol 2021; 9: 619330.
[http://dx.doi.org/10.3389/fcell.2021.619330] [PMID: 34012960]
[14]
He B, Lang J, Wang B, et al. TOOme: A novel computational framework to infer cancer tissue-of-origin by integrating both gene mutation and expression. Front Bioeng Biotechnol 2020; 8: 394.
[http://dx.doi.org/10.3389/fbioe.2020.00394] [PMID: 32509741]
[15]
Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: Are the answers in sight? Nat Rev Genet 2008; 9(2): 102-14.
[http://dx.doi.org/10.1038/nrg2290] [PMID: 18197166]
[16]
Mohr A, Mott J. Overview of microRNA biology. Semin Liver Dis 2015; 35(1): 003-11.
[http://dx.doi.org/10.1055/s-0034-1397344] [PMID: 25632930]
[17]
Xu J, Zhu W, Cai L, et al. LRMCMDA: Predicting miRNAdisease association by integrating low-rank matrix completion with miRNA and disease similarity information. IEEE Access 2020; 8: 80728-38.
[http://dx.doi.org/10.1109/ACCESS.2020.2990533]
[18]
Li X, Lin Y, Gu C, Yang J. FCMDAP: Using miRNA family and cluster information to improve the prediction accuracy of disease related miRNAs. BMC Syst Biol 2019; 13 (Suppl. 2): 26.
[http://dx.doi.org/10.1186/s12918-019-0696-9] [PMID: 30953512]
[19]
Xu J, Cai L, Liao B, et al. Identifying potential miRNAs–disease associations with probability matrix factorization. Front Genet 2019; 10: 1234.
[http://dx.doi.org/10.3389/fgene.2019.01234] [PMID: 31921290]
[20]
Yao Y, Ji B, Shi S, et al. IMDAILM: Inferring miRNA-disease association by integrating lncRNA and miRNA data. IEEE Access 2020; 8: 16517-27.
[http://dx.doi.org/10.1109/ACCESS.2019.2958055]
[21]
Ameres SL, Zamore PD. Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol 2013; 14(8): 475-88.
[http://dx.doi.org/10.1038/nrm3611] [PMID: 23800994]
[22]
Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 2005; 123(4): 631-40.
[http://dx.doi.org/10.1016/j.cell.2005.10.022] [PMID: 16271387]
[23]
Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science 2001; 294(5543): 853-8.
[http://dx.doi.org/10.1126/science.1064921] [PMID: 11679670]
[24]
Jansson MD, Lund AH. MicroRNA and cancer. Mol Oncol 2012; 6(6): 590-610.
[http://dx.doi.org/10.1016/j.molonc.2012.09.006] [PMID: 23102669]
[25]
Jang K, Ahn H, Sim J, et al. Loss of microRNA-200a expression correlates with tumor progression in breast cancer. Transl Res 2014; 163(3): 242-51.
[http://dx.doi.org/10.1016/j.trsl.2013.11.005] [PMID: 24280074]
[26]
Markou A, Yousef GM, Stathopoulos E, Georgoulias V, Lianidou E. Prognostic significance of metastasis-related microRNAs in early breast cancer patients with a long follow-up. Clin Chem 2014; 60(1): 197-205.
[http://dx.doi.org/10.1373/clinchem.2013.210542] [PMID: 24132943]
[27]
Hafez MM, Hassan ZK, Zekri AR, et al. MicroRNAs and metastasis-related gene expression in Egyptian breast cancer patients. APJCP 2012; 13(2): 591-8.
[PMID: 22524830]
[28]
Cuiffo BG, Campagne A, Bell GW, et al. MSC-regulated microRNAs converge on the transcription factor FOXP2 and promote breast cancer metastasis. Cell Stem Cell 2014; 15(6): 762-74.
[http://dx.doi.org/10.1016/j.stem.2014.10.001] [PMID: 25515522]
[29]
Xia Y, Wei K, Yang FM, et al. miR-1260b, mediated by YY1, activates KIT signaling by targeting SOCS6 to regulate cell proliferation and apoptosis in NSCLC. Cell Death Dis 2019; 10(2): 112.
[http://dx.doi.org/10.1038/s41419-019-1390-y] [PMID: 30737371]
[30]
Xu L, Li L, Li J, et al. Overexpression of miR-1260b in non-small cell lung cancer is associated with lymph node metastasis. Aging Dis 2015; 6(6): 478-85.
[http://dx.doi.org/10.14336/AD.2015.0620] [PMID: 26618049]
[31]
Zhao J, Cao J, Zhou L, et al. MiR-1260b inhibitor enhances the chemosensitivity of colorectal cancer cells to fluorouracil by targeting PDCD4/IGF1. Oncol Lett 2018; 16(4): 5131-9.
[http://dx.doi.org/10.3892/ol.2018.9307] [PMID: 30250581]
[32]
Liu DR, Guan QL, Gao MT, Jiang L, Kang HX. miR-1260b is a potential prognostic biomarker in colorectal cancer. Med Sci Monit 2016; 22: 2417-23.
[http://dx.doi.org/10.12659/MSM.898733] [PMID: 27399918]
[33]
Hirata H, Hinoda Y, Shahryari V, et al. Correction: Genistein downregulates onco-miR-1260b and upregulates sFRP1 and Smad4 via demethylation and histone modification in prostate cancer cells. Br J Cancer 2018; 119(3): 388.
[http://dx.doi.org/10.1038/s41416-018-0146-2] [PMID: 29930252]
[34]
Hirata H, Hinoda Y, Shahryari V, et al. Genistein downregulates onco-miR-1260b and upregulates sFRP1 and Smad4 via demethylation and histone modification in prostate cancer cells. Br J Cancer 2014; 110(6): 1645-54.
[http://dx.doi.org/10.1038/bjc.2014.48] [PMID: 24504368]
[35]
Hirata H, Ueno K, Nakajima K, et al. Genistein downregulates onco-miR-1260b and inhibits Wnt-signalling in renal cancer cells. Br J Cancer 2013; 108(10): 2070-8.
[http://dx.doi.org/10.1038/bjc.2013.173] [PMID: 23591200]
[36]
Li X, Song H, Liu Z, Bi Y. miR-1260b promotes cell migration and invasion of hepatocellular carcinoma by targeting the regulator of G-protein signaling 22. Biotechnol Lett 2018; 40(1): 57-62.
[http://dx.doi.org/10.1007/s10529-017-2455-6] [PMID: 29038925]
[37]
Huang J, Shi T, Ma T, et al. CCDC134, a novel secretory protein, inhibits activation of ERK and JNK, but not p38 MAPK. Cell Mol Life Sci 2008; 65(2): 338-49.
[http://dx.doi.org/10.1007/s00018-007-7448-5] [PMID: 18087676]
[38]
Huang J, Xiao L, Gong X, et al. Cytokine-like molecule CCDC134 contributes to CD8⁺ T-cell effector functions in cancer immunotherapy. Cancer Res 2014; 74(20): 5734-45.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-3132] [PMID: 25125657]
[39]
Zhong J, Zhao M, Luo Q, et al. CCDC134 is down-regulated in gastric cancer and its silencing promotes cell migration and invasion of GES-1 and AGS cells via the MAPK pathway. Mol Cell Biochem 2013; 372(1-2): 1-8.
[http://dx.doi.org/10.1007/s11010-012-1418-4] [PMID: 23070808]
[40]
Huang Z, Yang J, Qiu W, et al. HAUS5 is a potential prognostic biomarker with functional significance in breast cancer. Front Oncol 2022; 12: 829777.
[http://dx.doi.org/10.3389/fonc.2022.829777] [PMID: 35280773]
[41]
Khordadmehr M, Shahbazi R, Ezzati H, Jigari-Asl F, Sadreddini S, Baradaran B. Key microRNAs in the biology of breast cancer; emerging evidence in the last decade. J Cell Physiol 2019; 234(6): 8316-26.
[http://dx.doi.org/10.1002/jcp.27716] [PMID: 30422324]
[42]
Imani S, Wu RC, Fu J. MicroRNA-34 family in breast cancer: From research to therapeutic potential. J Cancer 2018; 9(20): 3765-75.
[http://dx.doi.org/10.7150/jca.25576] [PMID: 30405848]
[43]
Zhang W, Liu HT. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res 2002; 12(1): 9-18.
[http://dx.doi.org/10.1038/sj.cr.7290105] [PMID: 11942415]
[44]
Wagner EF, Nebreda ÁR. Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer 2009; 9(8): 537-49.
[http://dx.doi.org/10.1038/nrc2694] [PMID: 19629069]
[45]
Thompson EW, Price JT. Mechanisms of tumour invasion and metastasis: Emerging targets for therapy. Expert Opin Ther Targets 2002; 6(2): 217-33.
[http://dx.doi.org/10.1517/14728222.6.2.217] [PMID: 12223082]
[46]
Yang WF, Wang SZ. Expression of CD1a, CD80, CD86 in dendritic cell of tumor tissue and regional lymph node in esophageal carcinoma. Chin J Cancer 2004; 23(2): 189-92.
[47]
Comes A, Rosso O, Orengo AM, et al. CD25+ regulatory T cell depletion augments immunotherapy of micrometastases by an IL-21-secreting cellular vaccine. J Immunol 2006; 176(3): 1750-8.
[http://dx.doi.org/10.4049/jimmunol.176.3.1750] [PMID: 16424205]
[48]
Song QK, Ren J, Zhou XN, et al. The prognostic value of peripheral CD4+CD25+ T lymphocytes among early stage and triple negative breast cancer patients receiving dendritic cells-cytokine induced killer cells infusion. Oncotarget 2015; 6(38): 41350-9.
[http://dx.doi.org/10.18632/oncotarget.5534] [PMID: 26462021]

Rights & Permissions Print Cite
Article Metrics
4
© 2024 Bentham Science Publishers | Privacy Policy