The Oncogenic Role of microRNA-130a/301a/454 in Human Colorectal Cancer via Targeting Smad4 Expression

Transforming growth factor (TGF)-β/Smad signaling plays an important role in colon cancer development, progression and metastasis. In this study we demonstrated that the microRNA-130a/301a/454 family is up-regulated in colon cancer tissues compared to paired adjacent normal mucosa, which share the same 3′-untranslational region (3′-UTR) binding seed sequence and are predicated to target Smad4. In colorectal cancer HCT116 and SW480 cells, overexpression of miRNA-130a/301a/454 mimics enhances cell proliferation and migration, while inhibitors of these miRNAs affect cell survival. The biological function of miRNA-130a/301a/454 on colon cancer cells is likely mediated by suppression of Smad4, and the up-regulation of the miRNAs is correlated with Smad4 down-regulation in human colon cancers. Collectively, these results suggest that miRNA-130a/301a/454 are novel oncogenic miRNAs contributing to colon tumorigenesis by regulating TGF-β/Smad signaling, which may have potential application in cancer therapy.

• Publication year

  2013

• Venue

  PLoS ONE

• Publication date

  2013-02-05

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pone.0055532PMID 23393589PMCID 3564758
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Supplementary Materials and Methods

  2013cited by this paper
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  2012cited by this paper
• miR‐301a promotes pancreatic cancer cell proliferation by directly inhibiting bim expression

  2012cited by this paper
• miRNA-130a targets ATG2B and DICER1 to inhibit autophagy and trigger killing of chronic lymphocytic leukemia cells.

  2012cited by this paper
• microRNA-365, down-regulated in colon cancer, inhibits cell cycle progression and promotes apoptosis of colon cancer cells by probably targeting Cyclin D1 and Bcl-2.

  2012cited by this paper
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• Functional screening for miRNAs targeting Smad4 identified miR-199a as a negative regulator of TGF-β signalling pathway

  2012cited by this paper
• MicroRNA-301 mediates proliferation and invasion in human breast cancer.

  2011cited by this paper
• MicroRNAs 130a/b are regulated by BCR-ABL and downregulate expression of CCN3 in CML

  2011cited by this paper
• Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency.

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  2011cited by this paper
• Comparison of inflammatory microRNA expression in healthy and periodontitis tissues.

  2011cited by this paper
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  2011cited by this paper
• Increased miR-146a in gastric cancer directly targets SMAD4 and is involved in modulating cell proliferation and apoptosis.

  2011cited by this paper
• miRNA screening reveals a new miRNA family stimulating iPS cell generation via regulation of Meox2

  2011cited by this paper
• miR‐301a as an NF‐κB activator in pancreatic cancer cells

  2011cited by this paper
• Initial study of microRNA expression profiles of colonic cancer without lymph node metastasis

  2010cited by this paper
• Antimetastatic role of Smad4 signaling in colorectal cancer.

  2010cited by this paper
• Expression of miRNA-130a in Nonsmall Cell Lung Cancer

  2010cited by this paper
• microRNA-195 promotes apoptosis and suppresses tumorigenicity of human colorectal cancer cells.

  2010cited by this paper
• A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts.

  2010cited by this paper
• Smad Ubiquitylation Regulatory Factor 1/2 (Smurf1/2) Promotes p53 Degradation by Stabilizing the E3 Ligase MDM2*

  2010cited by this paper
• Regulation of somatic cell reprogramming through inducible mir-302 expression

  2010cited by this paper
• Over- and under-expressed microRNAs in human colorectal cancer.

  2009cited by this paper
• High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells.

  2009cited by this paper
• Embryonic stem cell–specific microRNAs promote induced pluripotency

  2009cited by this paper
• MicroRNAs in colorectal cancer: translation of molecular biology into clinical application

  2009cited by this paper
• Toluene exposure during the brain growth spurt reduced behavioral responses to nicotine in young adult rats: a potential role for nicotinic acetylcholine receptors in fetal solvent syndrome.

  2008cited by this paper
• Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5.

  2008cited by this paper
• Regulation of the Germinal Center Response by MicroRNA-155

  2007cited by this paper
• Cancer Statistics, 2007

  2007cited by this paper
• Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues

  2006cited by this paper
• MicroRNA signatures in human cancers

  2006cited by this paper
• Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

  2006cited by this paper
• Ribo-gnome: The Big World of Small RNAs

  2005cited by this paper
• MicroRNA function: multiple mechanisms for a tiny RNA?

  2005cited by this paper
• A pancreatic islet-specific microRNA regulates insulin secretion

  2004cited by this paper
• bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila.

  2003cited by this paper
• Higher frequency of Smad4 gene mutation in human colorectal cancer with distant metastasis

  1999cited by this paper
• Mutations of the DPC4/Smad4 gene in biliary tract carcinoma.

  1998cited by this paper
• Colorectal cancer

  1993cited by this paper
• Cancer statistics

  1989cited by this paper

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  2025cites this paper
• Regulatory crosstalk between TGF-β signaling and miRNAs: a head and neck cancer perspective

  2024cites this paper
• Recent advances and molecular mechanisms of TGF-β signaling in colorectal cancer, with focus on bioactive compounds targeting.

  2024cites this paper
• Comprehensive analysis of miRNA-mRNA regulatory pairs associated with colorectal cancer and the role in tumor immunity

  2023cites this paper
• The Expression Level and Mechanism of miRNAs in Non-Small Cell Lung Cancer

  2023cites this paper
• Exosomal circ_PTPRA inhibits tumorigenesis and promotes radiosensitivity in colorectal cancer by enriching the level of SMAD4 via competitively binding to miR-671-5p

  2022cites this paper
• Diagnostic Value of Potential MicroRNAs in CRC: A Meta-Analysis.

  2022cites this paper
• Mechanisms of Natural Extracts of Andrographis paniculata That Target Lipid-Dependent Cancer Pathways: A View from the Signaling Pathway

  2022cites this paper
• microRNAs: Small molecules with a large impact on colorectal cancer

  2021cites this paper
• Oxyresveratrol inhibits human colon cancer cell migration through regulating epithelial-mesenchymal transition and microRNA.

  2021cites this paper
• Suppression of MiR130a-3p Using CRISPR/Cas9 Induces Proliferation and Migration of Non-Small Cell Lung Cancer Cell Line

  2021cites this paper
• Simultaneous learning of individual microRNA-gene interactions and regulatory comodules

  2021cites this paper
• miR-454 performs tumor-promoting effects in oral squamous cell carcinoma via reducing NR3C2.

  2020cites this paper
• MiR-130a/Ndrg2 Axis Inhibits the Proliferation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis

  2020cites this paper
• Upregulation of miRNA-301a-3p promotes tumor progression in gastric cancer by suppressing NKRF and activating NF-κB signaling

  2020cites this paper
• Research on mechanism of miR-130a in regulating autophagy of bladder cancer cells through CYLD.

  2020cites this paper
• Clinical and In Silico Outcomes of miR-130a-5p and miR-615-3p Expression in Tumor Compared with Non-Tumor Adjacent Tissues of Patients with BC.

  2020cites this paper
• miR-301a promotes lung tumorigenesis by suppressing Runx3

  2019cites this paper
• Serum overexpression of miR-301a and miR-23a in patients with colorectal cancer

  2019cites this paper
• Role of TGF‐β signaling regulatory microRNAs in the pathogenesis of colorectal cancer

  2019cites this paper
• MiR-708-5p inhibits the progression of pancreatic ductal adenocarcinoma by targeting Sirt3.

  2019cites this paper
• The lncRNA HOXA11-AS promotes glioma cell growth and metastasis by targeting miR-130a-5p/HMGB2.

  2019cites this paper
• Identification of miRNAs correlating with stage and progression of colorectal cancer

  2019cites this paper
• A set of microRNAs coordinately controls tumorigenesis, invasion, and metastasis

  2019cites this paper
• Silencing Smad4 attenuates sensitivity of colorectal cancer cells to cetuximab by promoting epithelial-mesenchymal transition

  2019cites this paper
• MicroRNA-454 enhances proliferation and migration in non-small cell lung cancer cells

  2019cites this paper
• miR-454-3p promotes proliferation and induces apoptosis in human cervical cancer cells by targeting TRIM3.

  2019cites this paper
• MicroRNA-454-3p inhibits cervical cancer cell invasion and migration by targeting c-Met

  2018cites this paper
• MicroRNA-301a-3p suppressed the progression of hepatocellular carcinoma via targeting VGLL4.

  2018cites this paper
• Association between Altered Expression and Genetic Variations of Transforming Growth Factor β-Smad Pathway with Chronic Myeloid Leukemia

  2018cites this paper
• miR-3147 serves as an oncomiR in vulvar squamous cell cancer via Smad4 suppression

  2018cites this paper
• MicroRNAs as novel biomarkers for colorectal cancer: New outlooks.

  2018cites this paper
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  2018cites this paper
• Effects of miRNA-130a on the proliferation and apoptosis of glioma cell lines

  2018cites this paper
• Downregulation of miR-130a promotes cell growth and epithelial to mesenchymal transition by activating HMGB2 in glioma.

  2017cites this paper
• Anti-leukemic activity of microRNA-26a in a chronic lymphocytic leukemia mouse model

  2017cites this paper
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  2017cites this paper
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  2017cites this paper
• Changes in microRNA expression in response to Schistosoma japonicum infection

  2017cites this paper
• Identifying factors associated with the direction and significance of microRNA tumor-normal expression differences in colorectal cancer

  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
• MicroRNA expression profiling in patients with hepatocellular carcinoma of familial aggregation and hepatitis B virus infection.

  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2016cites this paper
• Identifying microRNA panels specifically associated with hepatocellular carcinoma and its different etiologies.

  2016cites this paper
• MicroRNA networks in pulmonary arterial hypertension: share mechanisms with cancer?

  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
• MiR-454 promotes the progression of human non-small cell lung cancer and directly targets PTEN.

  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
• International Journal of Cancer and Oncology

  2015cites this paper
• Cellular signaling pathways implicated in metastasis of colorectal cancer and the associated targeted agents.

  2015cites this paper
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  2015cites this paper
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  2015cites this paper
• MicroRNA-301a-3p promotes pancreatic cancer progression via negative regulation of SMAD4

  2015cites this paper
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  2015cites this paper
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  2015cites this paper
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  2015cites this paper
• Insights into the Role of microRNAs in Pancreatic Cancer Pathogenesis: Potential for Diagnosis, Prognosis, and Therapy.

  2015cites this paper
• Clinical implications of miRNAs in the pathogenesis, diagnosis and therapy of pancreatic cancer.

  2015cites this paper
• MicroRNA–mRNA interactions in colorectal cancer and their role in tumor progression

  2015influential citation
• Cooperative target mRNA destabilization and translation inhibition by miR-58 microRNA family in C. elegans

  2015cites this paper
• Role of cancer-associated fibroblasts in invasion and metastasis of gastric cancer.

  2015cites this paper
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  2015cites this paper
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  2015cites this paper
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  2015cites this paper
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  2015cites this paper
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  2015influential citation
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  2015cites this paper
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  2015cites this paper
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  2014influential citation
• MicroRNAs in colorectal cancer as markers and targets: Recent advances.

  2014cites this paper
• miR-320a suppresses colorectal cancer progression by targeting Rac1.

  2014cites this paper
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  2014cites this paper
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  2014cites this paper
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  2014cites this paper
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  2014cites this paper
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  2014influential citation
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  2014cites this paper
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  2014cites this paper
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  2013cites this paper