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
BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

miR-663a inhibits tumor growth and invasion by regulating TGF-β1 in hepatocellular carcinoma

Authors: Chengshuo Zhang, Baomin Chen, Ao Jiao, Feng Li, Ning Sun, Guoqing Zhang, Jialin Zhang

Published in: BMC Cancer | Issue 1/2018

Login to get access

Abstract

Background

The dysregulation of miR-663a is frequently observed in many human cancers. However, the functional role and precise mechanism of miR-663a have been controversial in hepatocellular carcinoma (HCC) and need to be studied in depth.

Methods

The expression of miR-663a was detected in human cell lines and HCC tissues by quantitative RT-PCR (qRT-PCR), and data from the Cancer Genome Atlas (TCGA). Cell proliferation was investigated using MTS, EdU, colony formation assays, and xenograft animal experiments, and the cell invasion capacity was evaluated using the transwell assay. The target gene of miR-663a was identified by qRT-PCR, Western blot, and dual-luciferase reporter assays. The clinicopathological features of miR-663a and the correlation between miR-663a and TGF-β1 expression were also investigated in the clinical samples of HCC.

Results

miR-663a was significantly downregulated in HCC cells relative to immortal normal liver cells, as indicated using qRT-PCR, and the lower expression of miR-663a was also confirmed in HCC tissue samples and the data from TCGA. The expression of miR-663a in HCC tissue samples was statistically significantly associated with size and the number of tumors. In addition, the upregulation of miR-663a inhibited the proliferation and invasion of HCC cells in vitro. Further study showed that miR-663a directly targeted transforming growth factor beta 1 (TGF-β1) to suppress HCC invasion, and that the inhibitory effect of miR-663a on cell invasion could be regulated by TGF-β1. In vivo studies showed that miR-663a significantly inhibited tumor growth. A negative correlation between miR-663a and TGF-β1 expression was also confirmed from the clinical samples of HCC.

Conclusions

miR-663a acts as a tumor suppressor and exerts a substantial role in inhibiting the proliferation, invasion, and tumorigenesis of HCC by regulating TGF-β1 in vitro and in vivo. These observations indicate that miR-663a may be a suitable diagnostic, therapeutic, and prognostic target for the treatment of HCC.
Appendix
Available only for authorised users
Literature
1.
Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32.CrossRef
2.
Rossi L, Zoratto F, Papa A, Iodice F, Minozzi M, Frati L, et al. Current approach in the treatment of hepatocellular carcinoma. World J Gastrointest Oncol. 2010;2(9):348–59.CrossRef
3.
Zhang CS, Zhang JL, Li XH, Li L, Li X, Zhou XY. Is radiofrequency ablation equal to surgical re-resection for recurrent hepatocellular carcinoma meeting the Milan criteria? A meta-analysis. J BUON. 2015;20(1):223–30.PubMed
4.
Zhang J, Chong CC, Chen GG, Lai PB. A seven-microRNA expression signature predicts survival in hepatocellular carcinoma. PLoS One. 2015;10(6):e0128628.CrossRef
5.
Zhang R, Liu C, Niu Y, Jing Y, Zhang H, Wang J, et al. MicroRNA-128-3p regulates mitomycin C-induced DNA damage response in lung cancer cells through repressing SPTAN1. Oncotarget. 2017;8(35):58098–107.PubMed
6.
Zhao H, Yu X, Ding Y, Zhao J, Wang G, Wu X, et al. MiR-770-5p inhibits cisplatin chemoresistance in human ovarian cancer by targeting ERCC2. Oncotarget. 2016;7(33):53254–68.CrossRef
7.
Lin M, Shi C, Lin X, Pan J, Shen S, Xu Z, et al. sMicroRNA-1290 inhibits cells proliferation and migration by targeting FOXA1 in gastric cancer cells. Gene. 2016;582(2):137–42.CrossRef
8.
Zhao D, Sui Y, Zheng X. MiR-331-3p inhibits proliferation and promotes apoptosis by targeting HER2 through the PI3K/Akt and ERK1/2 pathways in colorectal cancer. Oncol Rep. 2016;35(2):1075–82.CrossRef
9.
Zhu W, Qian J, Ma L, Ma P, Yang F, Shu Y. MiR-346 suppresses cell proliferation through SMYD3 dependent approach in hepatocellular carcinoma. Oncotarget. 2017;8(39):65218–29.PubMedPubMedCentral
10.
Gu X, Xue JQ, Han SJ, Qian SY, Zhang WH. Circulating microRNA-451 as a predictor of resistance to neoadjuvant chemotherapy in breast cancer. Cancer Biomark. 2016;16(3):395–403.CrossRef
11.
Jian P, Li ZW, Fang TY, Jian W, Zhuan Z, Mei LX, et al. Retinoic acid induces HL-60 cell differentiation via the upregulation of miR-663. J Hematol Oncol. 2011;4:20.CrossRef
12.
Ni CW, Qiu H, Jo H. MicroRNA-663 upregulated by oscillatory shear stress plays a role in inflammatory response of endothelial cells. Am J Physiol Heart Circ Physiol. 2011;300(5):H1762–9.CrossRef
13.
Tili E, Michaille JJ, Adair B, Alder H, Limagne E, Taccioli C, et al. Resveratrol decreases the levels of miR-155 by upregulating miR-663, a microRNA targeting JunB and JunD. Carcinogenesis. 2010;31(9):1561–6.CrossRef
14.
Carden T, Singh B, Mooga V, Bajpai P, Singh KK. Epigenetic modification of miR-663 controls mitochondria-to-nucleus retrograde signaling and tumor progression. J Biol Chem. 2017;292(50):20694-706.CrossRef
15.
Shi Y, Chen C, Zhang X, Liu Q, Xu JL, Zhang HR, et al. Primate-specific miR-663 functions as a tumor suppressor by targeting PIK3CD and predicts the prognosis of human glioblastoma. Clin Cancer Res. 2014;20(7):1803–13.CrossRef
16.
Shi Y, Chen C, Yu SZ, Liu Q, Rao J, Zhang HR, et al. miR-663 suppresses oncogenic function of CXCR4 in glioblastoma. Clin Cancer Res. 2015;21(17):4004–13.CrossRef
17.
Wang Z, Zhang H, Zhang P, Dong W, He L. MicroRNA-663 suppresses cell invasion and migration by targeting transforming growth factor beta 1 in papillary thyroid carcinoma. Tumour Biol. 2016;37(6):7633–44.CrossRef
18.
Pan J, Hu H, Zhou Z, Sun L, Peng L, Yu L, et al. Tumor-suppressive mir-663 gene induces mitotic catastrophe growth arrest in human gastric cancer cells. Oncol Rep. 2010;24(1):105–12.PubMed
19.
Yi C, Wang Q, Wang L, Huang Y, Li L, Liu L, et al. MiR-663, a microRNA targeting p21(WAF1/CIP1), promotes the proliferation and tumorigenesis of nasopharyngeal carcinoma. Oncogene. 2012;31(41):4421–33.CrossRef
20.
Liu ZY, Zhang GL, Wang MM, Xiong YN, Cui HQ. MicroRNA-663 targets TGFB1 and regulates lung cancer proliferation. Asian Pac J Cancer Prev. 2011;12(11):2819–23.PubMed
21.
Jiao L, Deng Z, Xu C, Yu Y, Li Y, Yang C, et al. miR-663 induces castration-resistant prostate cancer transformation and predicts clinical recurrence. J Cell Physiol. 2014;229(7):834–44.CrossRef
22.
Huang W, Li J, Guo X, Zhao Y, Yuan X. miR-663a inhibits hepatocellular carcinoma cell proliferation and invasion by targeting HMGA2. Biomed Pharmacother. 2016;81:431–8.CrossRef
23.
Huang Y, Liu J, Fan L, Wang F, Yu H, Wei W, et al. miR-663 overexpression induced by endoplasmic reticulum stress modulates hepatocellular carcinoma cell apoptosis via transforming growth factor beta 1. Onco Targets Ther. 2016;9:1623–33.CrossRef
24.
Dweep H, Sticht C, Pandey P, Gretz N. miRWalk--database: prediction of possible miRNA binding sites by "walking" the genes of three genomes. J Biomed Inform. 2011;44(5):839–47.CrossRef
25.
Koudelkova P, Costina V, Weber G, Dooley S, Findeisen P, Winter P, et al. Transforming Growth Factor-beta Drives the Transendothelial Migration of Hepatocellular Carcinoma Cells. Int J Mol Sci. 2017;18(10).
26.
Peng L, Yuan XQ, Zhang CY, Ye F, Zhou HF, Li WL, et al. High TGF-beta1 expression predicts poor disease prognosis in hepatocellular carcinoma patients. Oncotarget. 2017;8(21):34387–97.CrossRef
27.
Forner A, Reig ME, de Lope CR, Bruix J. Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis. 2010;30(1):61–74.CrossRef
28.
Chang S, Chen B, Wang X, Wu K, Sun Y. Long non-coding RNA XIST regulates PTEN expression by sponging miR-181a and promotes hepatocellular carcinoma progression. BMC Cancer. 2017;17(1):248.CrossRef
29.
Wu G, Zheng KM, Xia SG, Wang YW, Meng XY, Qin XM, et al. MicroRNA-655-3p functions as a tumor suppressor by regulating ADAM10 and β-catenin pathway in hepatocellular carcinoma. J Exp Clin Cancer Res. 2016;35(89):12.PubMedPubMedCentral
30.
Vislovukh A, Kratassiouk G, Porto E, Gralievska N, Beldiman C, Pinna G, et al. Proto-oncogenic isoform A2 of eukaryotic translation elongation factor eEF1 is a target of miR-663 and miR-744. Br J Cancer. 2013;108(11):2304–11.CrossRef
31.
Kuroda K, Fukuda T, Krstic-Demonacos M, Demonacos C, Okumura K, Isogai H, et al. miR-663a regulates growth of colon cancer cells, after administration of antimicrobial peptides, by targeting CXCR4-p21 pathway. BMC Cancer. 2017;17(1):33.CrossRef
32.
Tili E, Michaille JJ, Alder H, Volinia S, Delmas D, Latruffe N, et al. Resveratrol modulates the levels of microRNAs targeting genes encoding tumor-suppressors and effectors of TGFbeta signaling pathway in SW480 cells. Biochem Pharmacol. 2010;80(12):2057–65.CrossRef
33.
Mody HR, Hung SW, AlSaggar M, Griffin J, Govindarajan R. Inhibition of S-Adenosylmethionine-dependent methyltransferase attenuates TGFbeta1-induced EMT and metastasis in pancreatic Cancer: putative roles of miR-663a and miR-4787-5p. Mol Cancer Res. 2016;14(11):1124–35.CrossRef
34.
Zang W, Wang Y, Wang T, Du Y, Chen X, Li M, et al. miR-663 attenuates tumor growth and invasiveness by targeting eEF1A2 in pancreatic cancer. Mol Cancer. 2015;14:37.CrossRef
35.
Lin MS, Chen WC, Huang JX, Gao HJ, Sheng HH. Aberrant expression of microRNAs in serum may identify individuals with pancreatic cancer. Int J Clin Exp Med. 2014;7(12):5226–34.PubMedPubMedCentral
36.
Li Q, Cheng Q, Chen Z, Peng R, Chen R, Ma Z, et al. MicroRNA-663 inhibits the proliferation, migration and invasion of glioblastoma cells via targeting TGF-beta1. Oncol Rep. 2016;35(2):1125–34.CrossRef
37.
Wang S, Liu J, Li C, Yang X. Research of the effect of miR-663 on the proliferation of prostate cancer cells, and the correlations of miR-663 with pathological grade and clinical stage. J BUON. 2017;22(4):1011–6.PubMed
38.
Knyazev EN, Samatov TR, Fomicheva KA, Nyushko KM, Alekseev BY, Shkurnikov MY. MicroRNA hsa-miR-4674 in hemolysis-free blood plasma is associated with distant metastases of prostatic Cancer. Bull Exp Biol Med. 2016;161(1):112–5.CrossRef
39.
Liang S, Zhang N, Deng Y, Chen L, Zhang Y, Zheng Z, et al. miR-663 promotes NPC cell proliferation by directly targeting CDKN2A. Mol Med Rep. 2017;16(4):4863–70.CrossRef
40.
Liang S, Zhang N, Deng Y, Chen L, Zhang Y, Zheng Z, et al. Increased serum level of MicroRNA-663 is correlated with poor prognosis of patients with nasopharyngeal carcinoma. Dis Markers. 2016;2016:7648215.CrossRef
41.
Wang G, Dong F, Xu Z, Sharma S, Hu X, Chen D, et al. MicroRNA profile in HBV-induced infection and hepatocellular carcinoma. BMC Cancer. 2017;17(1):805.CrossRef
42.
Tian M, Schiemann WP. The TGF-beta paradox in human cancer: an update. Future Oncol. 2009;5(2):259–71.CrossRef
43.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.CrossRef
44.
Wang H, Jiang Y, Peng H, Chen Y, Zhu P, Huang Y. Recent progress in microRNA delivery for cancer therapy by non-viral synthetic vectors. Adv Drug Deliv Rev. 2015;81:142–60.CrossRef
Metadata
Title
miR-663a inhibits tumor growth and invasion by regulating TGF-β1 in hepatocellular carcinoma
Authors
Chengshuo Zhang
Baomin Chen
Ao Jiao
Feng Li
Ning Sun
Guoqing Zhang
Jialin Zhang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-5016-z

Other articles of this Issue 1/2018

BMC Cancer 1/2018 Go to the issue

Research article

Application of Ventana immunocytochemical analysis on ThinPrep cytology slides for detection of ALK rearrangement in patients with advanced non–small-cell lung cancer

Research article

New pre-treatment eosinophil-related ratios as prognostic biomarkers for survival outcomes in endometrial cancer

Research article

Knowledge towards cervical cancer prevention and screening practices among women who attended reproductive and child health clinic at Magu district hospital, Lake Zone Tanzania: a cross-sectional study

Research article

What is the impact of rerouting a cancer diagnosis from emergency presentation to GP referral on resource use and survival? Evidence from a population-based study

Research article

Prognostic value of the fibrinogen/albumin ratio (FAR) in patients with operable soft tissue sarcoma

Research article

Breast magnetic resonance imaging for surveillance of women with a personal history of breast cancer: outcomes stratified by interval between definitive surgery and surveillance MR imaging
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