Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Molecular Cancer
Published in: Molecular Cancer 1/2018

Open Access 01-12-2018 | Research

MicroRNA-494 promotes cancer progression and targets adenomatous polyposis coli in colorectal cancer

Authors: Ying Zhang, Lu Guo, Yuhuan Li, Gui-Hai Feng, Fei Teng, Wei Li, Qi Zhou

Published in: Molecular Cancer | Issue 1/2018

Login to get access

Abstract

Background

Aberrant activation of the Wnt/β-catenin signaling pathway is frequently observed in colorectal cancer (CRC). β-catenin is the major Wnt signaling pathway effector and inactivation of adenomatous polyposis coli (APC) results in nuclear accumulation of β-catenin. It has been suggested that inactivation of APC plays an important role in activation of the Wnt/β-catenin pathway and in the progression of colorectal tumorigenesis. However, the mechanism through which APC mediates colorectal tumorigenesis is not understood. Increasing evidence suggests that the dysregulation of microRNAs (miRNAs) is involved in colorectal tumorigenesis. Although miR-494 has been reported as being an upregulated miRNA, the interplay between miR-494 and APC-mediated colorectal tumorigenesis progression remains unclear.

Methods

The expression of miR-494 in tissues from patients diagnosed with CRC was analyzed using a microarray and real-time PCR. The effects of miR-494 on cell proliferation and tumorigenesis in CRC cells were analyzed by flow cytometry, colony formation assays, BrdU incorporation assays, and CCK8 assays. The correlation between miR-494 expression and APC expression, as well as the mechanisms by which miR-494 regulates APC in CRC were also addressed.

Results

miR-494 was significantly upregulated in CRC tissues, and this increase was negatively associated with APC expression. APC was confirmed to be a direct target of miR-494 in CRC. Furthermore, overexpression of miR-494 induced Wnt/β-catenin signaling by targeting APC, thus promoting CRC cell growth.

Conclusions

This study provides novel insights into the role of miR-494 in controlling CRC cell proliferation and tumorigenesis, and identifies miR-494 as a potential prognostic marker and therapeutic target.
Literature
1.
Harrison S, Benziger H. The molecular biology of colorectal carcinoma and its implications: a review. Surgeon. 2011;9(4):200–10.CrossRefPubMed
2.
Pandurangan AK. Potential targets for prevention of colorectal cancer: a focus on PI3K/Akt/mTOR and Wnt pathways. Asian Pac J Cancer Prev. 2013;14(4):2201–5.CrossRefPubMed
3.
Miyaki M, et al. Characteristics of somatic mutation of the adenomatous polyposis coli gene in colorectal tumors. Cancer Res. 1994;54(11):3011–20.PubMed
4.
Powell SM, et al. APC mutations occur early during colorectal tumorigenesis. Nature. 1992;359(6392):235–7.CrossRefPubMed
5.
Coppede F, et al. Genetic and epigenetic biomarkers for diagnosis, prognosis and treatment of colorectal cancer. World J Gastroenterol. 2014;20(4):943–56.CrossRefPubMedPubMedCentral
6.
Morin PJ, et al. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997;275(5307):1787–90.CrossRefPubMed
7.
Munemitsu S, et al. Deletion of an amino-terminal sequence beta-catenin in vivo and promotes hyperphosporylation of the adenomatous polyposis coli tumor suppressor protein. Mol Cell Biol. 1996;16(8):4088–94.CrossRefPubMedPubMedCentral
8.
9.
Ikeda S, et al. Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. EMBO J. 1998;17(5):1371–84.CrossRefPubMedPubMedCentral
10.
Sancho E, Batlle E, Clevers H. Live and let die in the intestinal epithelium. Curr Opin Cell Biol. 2003;15(6):763–70.CrossRefPubMed
11.
Liu F, et al. Wnt-beta-catenin signaling initiates taste papilla development. Nat Genet. 2007;39(1):106–12.CrossRefPubMed
12.
13.
14.
He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5(7):522–31.CrossRefPubMed
15.
Song SJ, et al. MicroRNA-antagonism regulates breast cancer Stemness and metastasis via TET-family-dependent chromatin remodeling. Cell. 2013;154(2):311–24.CrossRefPubMedPubMedCentral
16.
Song SJ, et al. The Oncogenic MicroRNA miR-22 targets the TET2 tumor suppressor to promote hematopoietic stem cell self-renewal and transformation. Cell Stem Cell. 2013;13(1):87–101.CrossRefPubMedPubMedCentral
17.
Valencia-Sanchez MA, et al. Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev. 2006;20(5):515–24.CrossRefPubMed
18.
Miranda KC, et al. A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. Cell. 2006;126(6):1203–17.CrossRefPubMed
19.
20.
Voorhoeve PM, et al. A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell. 2006;124(6):1169–81.CrossRefPubMed
21.
Kayani M, et al. Role of miRNAs in breast cancer. Asian Pac J Cancer Prev. 2011;12(12):3175–80.PubMed
22.
23.
Zhang Y, et al. Hepatitis C virus-induced up-regulation of microRNA-155 promotes hepatocarcinogenesis by activating Wnt signaling. Hepatology. 2012;56(5):1631–40.CrossRefPubMed
24.
Asangani IA, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 2008;27(15):2128–36.CrossRefPubMed
25.
Huang Z, et al. MicroRNA-95 promotes cell proliferation and targets sorting Nexin 1 in human colorectal carcinoma. Cancer Res. 2011;71(7):2582–9.CrossRefPubMed
26.
Subramanian M, et al. MiR-29b downregulates canonical Wnt signaling by suppressing coactivators of beta-catenin in human colorectal cancer cells. J Cell Biochem. 2014;115(11):1974–84.PubMed
27.
Sun HB, et al. miR494 is an independent prognostic factor and promotes cell migration and invasion in colorectal cancer by directly targeting PTEN. Int J Oncol. 2014;45(6):2486–94.CrossRefPubMed
28.
29.
30.
Benetatos L, et al. The microRNAs within the DLK1-DIO3 genomic region: involvement in disease pathogenesis. Cell Mol Life Sci. 2013;70(5):795–814.CrossRefPubMed
31.
Farago M, et al. Kinase-inactive glycogen synthase kinase 3beta promotes Wnt signaling and mammary tumorigenesis. Cancer Res. 2005;65(13):5792–801.CrossRefPubMed
32.
Korinek V, et al. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC−/− colon carcinoma. Science. 1997;275(5307):1784–7.CrossRefPubMed
33.
Willert K, Nusse R. Beta-catenin: a key mediator of Wnt signaling. Curr Opin Genet Dev. 1998;8(1):95–102.CrossRefPubMed
34.
35.
36.
Xing Y, et al. Crystal structure of a beta-catenin/APC complex reveals a critical role for APC phosphorylation in APC function. Mol Cell. 2004;15(4):523–33.CrossRefPubMed
37.
Mikels AJ, Nusse R. Wnts as ligands: processing, secretion and reception. Oncogene. 2006;25(57):7461–8.CrossRefPubMed
38.
Angers S, Moon RT. Proximal events in Wnt signal transduction. Nat Rev Mol Cell Biol. 2009;10(7):468–77.CrossRefPubMed
39.
Liu L, et al. Overexpressed miR-494 down-regulates PTEN gene expression in cells transformed by anti-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide. Life Sci. 2010;86(5–6):192–8.CrossRefPubMed
40.
Liu Y, et al. MicroRNA-494 is required for the accumulation and functions of tumor-expanded myeloid-derived suppressor cells via targeting of PTEN. J Immunol. 2012;188(11):5500–10.CrossRefPubMed
41.
Romano G, et al. MiR-494 is regulated by ERK1/2 and modulates TRAIL-induced apoptosis in non-small-cell lung cancer through BIM down-regulation. Proc Natl Acad Sci U S A. 2012;109(41):16570–5.CrossRefPubMedPubMedCentral
42.
Lim L, et al. MiR-494 within an oncogenic MicroRNA megacluster regulates G1/S transition in liver tumorigenesis through suppression of MCC. Hepatology. 2013;59(1):202–15.
43.
Ohdaira H, et al. MicroRNA-494 suppresses cell proliferation and induces senescence in A549 lung cancer cells. Cell Prolif. 2012;45(1):32–8.CrossRefPubMed
44.
Olaru AV, et al. MicroRNA down-regulated in human cholangiocarcinoma control cell cycle through multiple targets involved in the G1/S checkpoint. Hepatology. 2011;54(6):2089–98.CrossRefPubMedPubMedCentral
Metadata
Title
MicroRNA-494 promotes cancer progression and targets adenomatous polyposis coli in colorectal cancer
Authors
Ying Zhang
Lu Guo
Yuhuan Li
Gui-Hai Feng
Fei Teng
Wei Li
Qi Zhou
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2018
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-017-0753-1

Other articles of this Issue 1/2018

Molecular Cancer 1/2018 Go to the issue

Review

Targeting few to help hundreds: JAK, MAPK and ROCK pathways as druggable targets in atypical chronic myeloid leukemia

Research

LncRNA PTAR promotes EMT and invasion-metastasis in serous ovarian cancer by competitively binding miR-101-3p to regulate ZEB1 expression

Research

AR–PDEF pathway promotes tumour proliferation and upregulates MYC-mediated gene transcription by promoting MAD1 degradation in ER-negative breast cancer

Research

LncRNA PVT1 triggers Cyto-protective autophagy and promotes pancreatic ductal adenocarcinoma development via the miR-20a-5p/ULK1 Axis

Research

Histone demethylase KDM4D promotes gastrointestinal stromal tumor progression through HIF1β/VEGFA signalling

Review

The role of YAP/TAZ activity in cancer metabolic reprogramming
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits