MiR-581/SMAD7 Axis Contributes to Colorectal Cancer Metastasis: A Bioinformatic and Experimental Validation-Based Study

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2020 Sep 9

PMID 32899503

Citations 8

Authors

Xiaojuan Zhao

Shuzhen Liu

Bianbian Yan

Jin Yang

Erfei Chen

Affiliations

Soon will be listed here.

Abstract

Metastasis is a well-known poor prognostic factor and primary cause of mortality in patients with colorectal cancer (CRC). Recently, with the progress of high through-put sequencing, aberrantly expressed non-coding RNAs (ncRNAs) were found to participate in the initiation and development of cancer. However, the mechanisms of ncRNA-mediated regulation of metastasis in CRC remain largely unknown. In this study, we systematically analyzed the expression network of microRNAs (miRNAs) and genes in CRC metastasis using bioinformatics, and discovered that the miR-581/SMAD7 axis could be a potential factor that drives CRC metastasis. A dual luciferase report assay and protein analysis confirmed the binding relationship between miR-581 and SMAD7. Further functional assays revealed that miR-581 inhibition could suppress cell proliferation and induce apoptosis in SW480 cells. Up-regulation or down-regulation of miR-581 could both affect cell invasion capacity and modulate epithelial to mesenchymal transition (EMT) via a SMAD7/TGFβ signaling pathway. In conclusion, our findings elucidated that miR-581/SMAD7 could be essential for CRC metastasis, and may serve as a potential therapeutic target for CRC patients.

Citing Articles

Synthesis and Regulation of miRNA, Its Role in Oncogenesis, and Its Association with Colorectal Cancer Progression, Diagnosis, and Prognosis.

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SMAD Proteins in TGF-β Signalling Pathway in Cancer: Regulatory Mechanisms and Clinical Applications.

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eEF1A1 promotes colorectal cancer progression and predicts poor prognosis of patients.

Fan A, Zhao X, Liu H, Li D, Guo T, Zhang J Cancer Med. 2022; 12(1):513-524.

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MicroRNAs Are Key Molecules Involved in the Gene Regulation Network of Colorectal Cancer.

Yang F, Xuan G, Chen Y, Cao L, Zhao M, Wang C Front Cell Dev Biol. 2022; 10:828128.

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References

Halder S, Beauchamp R, Datta P . Smad7 induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis. Exp Cell Res. 2005; 307(1):231-46. DOI: 10.1016/j.yexcr.2005.03.009. View

Tong L, Shen S, Huang Q, Fu J, Wang T, Pan L . Proteasome-dependent degradation of Smad7 is critical for lung cancer metastasis. Cell Death Differ. 2019; 27(6):1795-1806. PMC: 7244558. DOI: 10.1038/s41418-019-0459-6. View

Shi Z, Wu D, Tang R, Li X, Chen R, Xue S . Silencing of HMGA2 promotes apoptosis and inhibits migration and invasion of prostate cancer cells. J Biosci. 2016; 41(2):229-36. DOI: 10.1007/s12038-016-9603-3. View

Carvalho B, Irizarry R . A framework for oligonucleotide microarray preprocessing. Bioinformatics. 2010; 26(19):2363-7. PMC: 2944196. DOI: 10.1093/bioinformatics/btq431. View

Chen E, Yang F, He H, Li Q, Zhang W, Xing J . Alteration of tumor suppressor BMP5 in sporadic colorectal cancer: a genomic and transcriptomic profiling based study. Mol Cancer. 2018; 17(1):176. PMC: 6302470. DOI: 10.1186/s12943-018-0925-7. View

Feng F, Qiu H . RETRACTED: Effects of Artesunate on chondrocyte proliferation, apoptosis and autophagy through the PI3K/AKT/mTOR signaling pathway in rat models with rheumatoid arthritis. Biomed Pharmacother. 2018; 102:1209-1220. DOI: 10.1016/j.biopha.2018.03.142. View

Stolfi C, Marafini I, De Simone V, Pallone F, Monteleone G . The dual role of Smad7 in the control of cancer growth and metastasis. Int J Mol Sci. 2013; 14(12):23774-90. PMC: 3876077. DOI: 10.3390/ijms141223774. View

Fu Y, Tang Y, Wang J, Guo Z . MicroRNA-181c Suppresses the Biological Progression of Osteosarcoma via Targeting SMAD7 and Regulating Transforming Growth Factor-β (TGF-β) Signaling Pathway. Med Sci Monit. 2019; 25:4801-4810. PMC: 6612243. DOI: 10.12659/MSM.916939. View

Shirafkan N, Mansoori B, Mohammadi A, Shomali N, Ghasbi M, Baradaran B . MicroRNAs as novel biomarkers for colorectal cancer: New outlooks. Biomed Pharmacother. 2017; 97:1319-1330. DOI: 10.1016/j.biopha.2017.11.046. View

10.

Huang N, Li W, Wang X, Qi S . MicroRNA-17-5p aggravates lipopolysaccharide-induced injury in nasal epithelial cells by targeting Smad7. BMC Cell Biol. 2018; 19(1):1. PMC: 5809994. DOI: 10.1186/s12860-018-0152-5. View

11.

Chaudhry M, Omaruddin R, Brumbaugh C, Tariq M, Pourmand N . Identification of radiation-induced microRNA transcriptome by next-generation massively parallel sequencing. J Radiat Res. 2013; 54(5):808-22. PMC: 3766286. DOI: 10.1093/jrr/rrt014. View

12.

Chen E, Yang F, He H, Lei L, Liu R, Du L . Decreased level of RASSF6 in sporadic colorectal cancer and its anti-tumor effects both in vitro and in vivo. Oncotarget. 2016; 7(15):19813-23. PMC: 4991420. DOI: 10.18632/oncotarget.7852. View

13.

Zhou T, Yu L, Huang J, Zhao X, Li Y, Hu Y . GDF10 inhibits proliferation and epithelial-mesenchymal transition in triple-negative breast cancer via upregulation of Smad7. Aging (Albany NY). 2019; 11(10):3298-3314. PMC: 6555447. DOI: 10.18632/aging.101983. View

14.

Wang Y, Zhang P, Yuan M, Li X . Overexpression of miRNA-21 Promotes the Proliferation and Invasion in Hepatocellular Carcinoma Cells via Suppressing SMAD7. Technol Cancer Res Treat. 2019; 18:1533033819878686. PMC: 6763940. DOI: 10.1177/1533033819878686. View

15.

Guo C, Sah J, Beard L, Willson J, Markowitz S, Guda K . The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers. Genes Chromosomes Cancer. 2008; 47(11):939-46. PMC: 2739997. DOI: 10.1002/gcc.20596. View

16.

Ventura A, Jacks T . MicroRNAs and cancer: short RNAs go a long way. Cell. 2009; 136(4):586-91. PMC: 3910108. DOI: 10.1016/j.cell.2009.02.005. View

17.

Nicoloso M, Spizzo R, Shimizu M, Rossi S, Calin G . MicroRNAs--the micro steering wheel of tumour metastases. Nat Rev Cancer. 2009; 9(4):293-302. DOI: 10.1038/nrc2619. View

18.

Nabatchian F, Naiini M, Moradi A, Tabatabaeian H, Hoghoughi N, Azadeh M . miR-581-Related Single Nucleotide Polymorphism, rs2641726, Located in MUC4 Gene, is Associated with Gastric Cancer Incidence. Indian J Clin Biochem. 2019; 34(3):347-351. PMC: 6660594. DOI: 10.1007/s12291-018-0751-0. View

19.

Yuan L, Qian G, Chen L, Wu C, Dan H, Xiao Y . Co-expression Network Analysis of Biomarkers for Adrenocortical Carcinoma. Front Genet. 2018; 9:328. PMC: 6104177. DOI: 10.3389/fgene.2018.00328. View

20.

Nittka S, Bohm C, Zentgraf H, Neumaier M . The CEACAM1-mediated apoptosis pathway is activated by CEA and triggers dual cleavage of CEACAM1. Oncogene. 2008; 27(26):3721-8. DOI: 10.1038/sj.onc.1211033. View