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
Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2018

Open Access 01-12-2018 | Research

circFBLIM1 act as a ceRNA to promote hepatocellular cancer progression by sponging miR-346

Authors: Ning Bai, Eming Peng, Xingsheng Qiu, Ning Lyu, Zhejia Zhang, Yiming Tao, Xinying Li, Zhiming Wang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

Login to get access

Abstract

Backgroud

Accumulating evidences indicate that circular RNAs (circRNAs), a class of non-coding RNAs, play important roles in tumorigenesis. However, the function of circRNAs in hepatocellular cancer (HCC) is largely unknown.

Methods

We performed circRNA microarrays to identify circRNAs that are aberrantly expressed in HCC tissues. Expression levels of a significantly upregulated circRNA, circFBLIM1, was detected by quantitative real-time PCR (qRT-PCR) in HCC cell lines and tissues. Then, we examined the functions of circFBLIM1 in HCC by cell proliferation, apoptosis, invasion and mouse xenograft assay. In addition, luciferase assay and RNA immunoprecipitation (RIP) assay were used to explore the miRNA sponge function of circFBLIM1 in HCC.

Results

Microarray analysis and qRT-PCR verified a circRNA termed circFBLIM1 that was upregulated in HCC tissues and cell lines. Knockdown of circFBLIM1 inhibited proliferation, invasion and promoted apoptosis in HCC. Via luciferase reporter assays, circFBLIM1 and FBLIM1 were observed to directly bind to miR-346. Subsequent experiments showed that circFBLIM1 and FBLIM1 regulated the expression of each other by sponging miR-346.

Conclusions

Taken together, we conclude that circFBLIM1 may function as a competing endogenous RNA (ceRNA) to regulate FBLIM1 expression through sponging miR-346 to exert regulatory functions in HCC. circFBLIM1 may be a diagnostic biomarker and potential target for HCC therapy.
Literature
1.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.CrossRefPubMed
2.
3.
Mikhail S, Cosgrove D, Zeidan A. Hepatocellular carcinoma: systemic therapies and future perspectives. Expert Rev Anticancer Ther. 2014;14(10):1205–18.CrossRefPubMed
4.
5.
6.
7.
Yao Z, Luo J, Hu K, Lin J, Huang H, Wang Q, et al. ZKSCAN1 gene and its related circular RNA (circZKSCAN1) both inhibit hepatocellular carcinoma cell growth, migration, and invasion but through different signaling pathways. Mol Oncol. 2017;11(4):422–37.CrossRefPubMedPubMedCentral
8.
Han D, Li J, Wang H, Su X, Hou J, Gu Y, et al. Circular RNA circMTO1 acts as the sponge of microRNA-9 to suppress hepatocellular carcinoma progression. Hepatology. 2017;66(4):1151–64.CrossRefPubMed
9.
10.
D'Anzeo M, Faloppi L, Scartozzi M, Giampieri R, Bianconi M, Del Prete M, et al. The role of micro-RNAs in hepatocellular carcinoma: from molecular biology to treatment. Molecules. 2014;19(5):6393–406.CrossRefPubMed
11.
Hung CH, Chiu YC, Chen CH, Hu TH. MicroRNAs in hepatocellular carcinoma: carcinogenesis, progression, and therapeutic target. Biomed Res Int. 2014;2014:486407.PubMedPubMedCentral
12.
13.
14.
15.
Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495(7441):384–8.CrossRefPubMed
16.
Zhong Z, Huang M, Lv M, He Y, Duan C, Zhang L, et al. Circular RNA MYLK as a competing endogenous RNA promotes bladder cancer progression through modulating VEGFA/VEGFR2 signaling pathway. Cancer Lett. 2017;403:305–17.CrossRefPubMed
17.
Rasool M, Rashid S, Arooj M, Ansari SA, Khan KM, Malik A, et al. New possibilities in hepatocellular carcinoma treatment. Anticancer Res. 2014;34(4):1563–71.PubMed
18.
Chen LL. The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol. 2016;17(4):205–11.CrossRefPubMed
19.
Oskowitz AZ, Lu J, Penfornis P, Ylostalo J, McBride J, Flemington EK, et al. Human multipotent stromal cells from bone marrow and microRNA: regulation of differentiation and leukemia inhibitory factor expression. Proc Natl Acad Sci U S A. 2008;105(47):18372–7.CrossRefPubMedPubMedCentral
20.
Alsaleh G, Suffert G, Semaan N, Juncker T, Frenzel L, Gottenberg JE, et al. Bruton's tyrosine kinase is involved in miR-346-related regulation of IL-18 release by lipopolysaccharide-activated rheumatoid fibroblast-like synoviocytes. J Immunol. 2009;182(8):5088–97.CrossRefPubMed
21.
Weber F, Teresi RE, Broelsch CE, Frilling A, Eng C. A limited set of human MicroRNA is deregulated in follicular thyroid carcinoma. J Clin Endocrinol Metab. 2006;91(9):3584–91.CrossRefPubMed
22.
Wang Q, Cai J, Cai XH, Chen L. miR-346 regulates osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting the Wnt/beta-catenin pathway. PLoS One. 2013;8(9):e72266.CrossRefPubMedPubMedCentral
23.
Semaan N, Frenzel L, Alsaleh G, Suffert G, Gottenberg JE, Sibilia J, et al. miR-346 controls release of TNF-alpha protein and stability of its mRNA in rheumatoid arthritis via tristetraprolin stabilization. PLoS One. 2011;6(5):e19827.CrossRefPubMedPubMedCentral
24.
Guo J, Lv J, Liu M, Tang H. miR-346 up-regulates Argonaute 2 (AGO2) protein expression to augment the activity of other MicroRNAs (miRNAs) and contributes to cervical Cancer cell malignancy. J Biol Chem. 2015;290(51):30342–50.CrossRefPubMedPubMedCentral
25.
Xiao J, Liu D, Jiao W, Guo J, Wang X, Zhang X, et al. Effects of microRNA-346 on epithelial-mesenchymal transition in mouse podocytes. Gene. 2015;560(2):195–9.CrossRefPubMed
26.
Tu Y, Wu S, Shi X, Chen K, Wu C. Migfilin and Mig-2 link focal adhesions to filamin and the actin cytoskeleton and function in cell shape modulation. Cell. 2003;113(1):37–47.CrossRefPubMed
27.
Gkretsi V, Zhang Y, Tu Y, Chen K, Stolz DB, Yang Y, et al. Physical and functional association of migfilin with cell-cell adhesions. J Cell Sci. 2005;118(Pt 4):697–710.CrossRefPubMed
28.
Davidson B, Holth A, Nguyen MT, Trope CG, Wu C. Migfilin, alpha-parvin and beta-parvin are differentially expressed in ovarian serous carcinoma effusions, primary tumors and solid metastases. Gynecol Oncol. 2013;128(2):364–70.CrossRefPubMed
29.
Gkretsi V, Papanikolaou V, Zacharia LC, Athanassiou E, Wu C, Tsezou A. Mitogen-inducible Gene-2 (MIG2) and migfilin expression is reduced in samples of human breast cancer. Anticancer Res. 2013;33(5):1977–81.PubMed
30.
He H, Ding F, Li S, Chen H, Liu Z. Expression of migfilin is increased in esophageal cancer and represses the Akt-beta-catenin activation. Am J Cancer Res. 2014;4(3):270–8.PubMedPubMedCentral
31.
He H, Ding F, Li Y, Luo A, Chen H, Wu C, et al. Migfilin regulates esophageal cancer cell motility through promoting GSK-3beta-mediated degradation of beta-catenin. Mol Cancer Res. 2012;10(3):273–81.CrossRefPubMed
32.
Zhang Y, Tu Y, Gkretsi V, Wu C. Migfilin interacts with vasodilator-stimulated phosphoprotein (VASP) and regulates VASP localization to cell-matrix adhesions and migration. J Biol Chem. 2006;281(18):12397–407.CrossRefPubMed
33.
Ou Y, Ma L, Dong L, Ma L, Zhao Z, Ma L, et al. Migfilin protein promotes migration and invasion in human glioma through epidermal growth factor receptor-mediated phospholipase C-gamma and STAT3 protein signaling pathways. J Biol Chem. 2012;287(39):32394–405.CrossRefPubMedPubMedCentral
34.
Gkretsi V, Bogdanos DP. Experimental evidence of Migfilin as a new therapeutic target of hepatocellular carcinoma metastasis. Exp Cell Res. 2015;334(2):219–27.CrossRefPubMed
35.
Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013;495(7441):333–8.CrossRefPubMed
36.
37.
Zheng Q, Bao C, Guo W, Li S, Chen J, Chen B, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun. 2016;7:11215.CrossRefPubMedPubMedCentral
Metadata
Title
circFBLIM1 act as a ceRNA to promote hepatocellular cancer progression by sponging miR-346
Authors
Ning Bai
Eming Peng
Xingsheng Qiu
Ning Lyu
Zhejia Zhang
Yiming Tao
Xinying Li
Zhiming Wang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-018-0838-8

Other articles of this Issue 1/2018

Journal of Experimental & Clinical Cancer Research 1/2018 Go to the issue

Research

Regulation of tNOX expression through the ROS-p53-POU3F2 axis contributes to cellular responses against oxaliplatin in human colon cancer cells

Research

High expression of Ras-related protein 1A promotes an aggressive phenotype in colorectal cancer via PTEN/FOXO3/CCND1 pathway

Research

GPR119 agonist enhances gefitinib responsiveness through lactate-mediated inhibition of autophagy

Research

Phytosomal curcumin causes natural killer cell-dependent repolarization of glioblastoma (GBM) tumor-associated microglia/macrophages and elimination of GBM and GBM stem cells

Research

Ajuba inhibits hepatocellular carcinoma cell growth via targeting of β-catenin and YAP signaling and is regulated by E3 ligase Hakai through neddylation

Research

PHF8 upregulation contributes to autophagic degradation of E-cadherin, epithelial-mesenchymal transition and metastasis in hepatocellular carcinoma
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