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 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2018

Open Access 01-12-2018 | Primary Research

MiR-20a-5p suppresses tumor proliferation by targeting autophagy-related gene 7 in neuroblastoma

Authors: Yongbo Yu, Jie Zhang, Yaqiong Jin, Yeran Yang, Jin Shi, Feng Chen, Shujing Han, Ping Chu, Jie Lu, Huanmin Wang, Yongli Guo, Xin Ni

Published in: Cancer Cell International | Issue 1/2018

Login to get access

Abstract

Background

Neuroblastoma (NB) is the most common malignant tumor originating from the extracranial sympathetic nervous system in children. The molecular mechanisms underlying this disease are complex, and not completely understood.

Methods

Quantitative real-time PCR (qRT-PCR) was applied to quantify the expression of miR-20a-5p and its target gene ATG7 in clinical NB tissues. The biological function of miR-20a-5p and ATG7 in SH-SY5Y cells was investigated through in vitro studies (Real-Time cell kinetic analyzer, colony formation assay, caspase-Glo 3/7 assay and western blotting). The luciferase reporter assay was conducted to verify the biological relationship between miR-20a-5p and ATG7.

Results

Here we found that miR-20a-5p expression was significantly downregulated whereas its target autophagy-related gene 7 (ATG7) was increased along with clinical staging of NB progression. Correlation analysis showed that miR-20a-5p had a negative correlation trend with ATG7. In SH-SY5Y cells, forced expression of miR-20a-5p suppressed ATG7 expression, autophagy initiation and cellular proliferation while promoted apoptosis, suggesting a potential association between miR-20a-5p and ATG7. Further bioinformatic target prediction combined with protein expression and luciferase reporter assay verified that miR-20a-5p inhibited ATG7 by directly binding to its 3′-UTR, confirming the involvement of miR-20a-5p in the regulation of ATG7 in NB.

Conclusions

These results clarified that miR-20a-5p inhibited cell proliferation and promoted apoptosis through negative regulation of ATG7 and thus autophagy suppression in SH-SY5Y cells. Therefore, defining the context-specific roles of autophagy in NB and regulatory mechanisms involved will be critical for developing autophagy-targeted therapeutics against NB. Both miR-20a-5p and ATG7 would be potential therapeutic targets for future NB treatment.
Literature
1.
Matthay KK, Maris JM, Schleiermacher G, Nakagawara A, Mackall CL, Diller L, et al. Neuroblastoma. Nat Rev Dis Primers. 2016;2:16078.CrossRefPubMed
2.
3.
Pugh TJ, Morozova O, Attiyeh EF, Asgharzadeh S, Wei JS, Auclair D, et al. The genetic landscape of high-risk neuroblastoma. Nat Genet. 2013;45:279–84.CrossRefPubMedPubMedCentral
4.
Molenaar JJ, Koster J, Zwijnenburg DA, van Sluis P, Valentijn LJ, van der Ploeg I, et al. Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes. Nature. 2012;483:589–93.CrossRefPubMed
5.
Peifer M, Hertwig F, Roels F, Dreidax D, Gartlgruber M, Menon R, et al. Telomerase activation by genomic rearrangements in high-risk neuroblastoma. Nature. 2015;526:700–4.CrossRefPubMedPubMedCentral
6.
7.
Berindan-Neagoe I, Monroig PD, Pasculli B, Calin GA. MicroRNAome genome: a treasure for cancer diagnosis and therapy. Ca-Cancer J Clin. 2014;64:311–36.CrossRefPubMedPubMedCentral
8.
Iwakawa HO, Tomari Y. The functions of microRNAs: mRNA decay and translational repression. Trends Cell Biol. 2015;25:651–65.CrossRefPubMed
9.
10.
Cheng L, Yang T, Kuang Y, Kong B, Yu S, Shu H, et al. MicroRNA-23a promotes neuroblastoma cell metastasis by targeting CDH1. Oncol Lett. 2014;7:839–45.PubMedPubMedCentral
11.
Li Y, Li W, Zhang JG, Li HY, Li YM. Downregulation of tumor suppressor menin by miR-421 promotes proliferation and migration of neuroblastoma. Tumour Biol. 2014;35:10011–7.CrossRefPubMed
12.
Qu HX, Zheng LD, Pu JR, Mei H, Xiang X, Zhao X, et al. miRNA-558 promotes tumorigenesis and aggressiveness of neuroblastoma cells through activating the transcription of heparanase. Hum Mol Genet. 2015;24:2539–51.CrossRefPubMed
13.
Liu G, Xu Z, Hao D. MicroRNA451 inhibits neuroblastoma proliferation, invasion and migration by targeting macrophage migration inhibitory factor. Mol Med Rep. 2016;13:2253–60.CrossRefPubMed
14.
Huang D, Bian G, Pan Y, Han X, Sun Y, Wang Y, et al. MiR-20a-5p promotes radio-resistance by targeting Rab27B in nasopharyngeal cancer cells. Cancer Cell Int. 2017;17:32.CrossRefPubMedPubMedCentral
15.
Cheng D, Zhao S, Tang H, Zhang D, Sun H, Yu F, et al. MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4. Oncotarget. 2016;7:45199–213.CrossRefPubMedPubMedCentral
16.
Pu Y, Yi Q, Zhao F, Wang H, Cai W, Cai S. MiR-20a-5p represses multi-drug resistance in osteosarcoma by targeting the KIF26B gene. Cancer Cell Int. 2016;16:64.CrossRefPubMedPubMedCentral
17.
18.
19.
20.
Choi AM, Ryter SW, Levine B. Autophagy in human health and disease. N Engl J Med. 2013;368:651–62.CrossRefPubMed
21.
Galluzzi L, Pietrocola F, Bravo-San Pedro JM, Amaravadi RK, Baehrecke EH, Cecconi F, et al. Autophagy in malignant transformation and cancer progression. EMBO J. 2015;34:856–80.CrossRefPubMedPubMedCentral
22.
Chang Y, Yan W, He X, Zhang L, Li C, Huang H, et al. miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions. Gastroenterology. 2012;143(177–87):e8.
23.
Pan B, Feng B, Chen Y, Huang G, Wang R, Chen L, et al. MiR-200b regulates autophagy associated with chemoresistance in human lung adenocarcinoma. Oncotarget. 2015;6:32805–20.CrossRefPubMedPubMedCentral
24.
Belounis A, Nyalendo C, Le Gall R, Imbriglio TV, Mahma M, Teira P, et al. Autophagy is associated with chemoresistance in neuroblastoma. BMC Cancer. 2016;16:891.CrossRefPubMedPubMedCentral
25.
Liu Y, Song L. HMGB1-induced autophagy in Schwann cells promotes neuroblastoma proliferation. Int J Clin Exp Pathol. 2015;8:504–10.PubMedPubMedCentral
26.
Li Z, Yan S, Attayan N, Ramalingam S, Thiele CJ. Combination of an allosteric Akt inhibitor MK-2206 with etoposide or rapamycin enhances the antitumor growth effect in neuroblastoma. Clin Cancer Res. 2012;18:3603–15.CrossRefPubMed
27.
Radogna F, Cerella C, Gaigneaux A, Christov C, Dicato M, Diederich M. Cell type-dependent ROS and mitophagy response leads to apoptosis or necroptosis in neuroblastoma. Oncogene. 2016;35:3839–53.CrossRefPubMed
28.
Oberg K, Modlin IM, De Herder W, Pavel M, Klimstra D, Frilling A, et al. Consensus on biomarkers for neuroendocrine tumour disease. Lancet Oncol. 2015;16:e435–46.CrossRefPubMedPubMedCentral
29.
30.
Das G, Shravage BV, Baehrecke EH. Regulation and function of autophagy during cell survival and cell death. Cold Spring Harb Perspect Biol. 2012;4:a008813.CrossRefPubMedPubMedCentral
31.
Xiang X, Mei H, Zhao X, Pu J, Li D, Qu H, et al. miRNA-337-3p suppresses neuroblastoma progression by repressing the transcription of matrix metalloproteinase 14. Oncotarget. 2015;6:22452–66.CrossRefPubMedPubMedCentral
32.
Galluzzi L, Bravo-San Pedro JM, Vitale I, Aaronson SA, Abrams JM, Adam D, et al. Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death Differ. 2015;22:58–73.CrossRefPubMed
33.
34.
35.
Strohecker AM, Guo JY, Karsli-Uzunbas G, Price SM, Chen GJ, Mathew R, et al. Autophagy sustains mitochondrial glutamine metabolism and growth of BrafV600E-driven lung tumors. Cancer Discov. 2013;3:1272–85.CrossRefPubMed
36.
Levy J, Cacheux W, Bara MA, L’Hermitte A, Lepage P, Fraudeau M, et al. Intestinal inhibition of Atg7 prevents tumour initiation through a microbiome-influenced immune response and suppresses tumour growth. Nat Cell Biol. 2015;17:1062–73.CrossRefPubMed
37.
Comincini S, Allavena G, Palumbo S, Morini M, Durando F, Angeletti F, et al. microRNA-17 regulates the expression of ATG7 and modulates the autophagy process, improving the sensitivity to temozolomide and low-dose ionizing radiation treatments in human glioblastoma cells. Cancer Biol Ther. 2013;14:574–86.CrossRefPubMedPubMedCentral
38.
Wang IK, Sun KT, Tsai TH, Chen CW, Chang SS, Yu TM, et al. MiR-20a-5p mediates hypoxia-induced autophagy by targeting ATG16L1 in ischemic kidney injury. Life Sci. 2015;136:133–41.CrossRefPubMed
39.
Wu H, Wang F, Hu S, Yin C, Li X, Zhao S, et al. MiR-20a and miR-106b negatively regulate autophagy induced by leucine deprivation via suppression of ULK1 expression in C2C12 myoblasts. Cell Signal. 2012;24:2179–86.CrossRefPubMed
40.
Green DR, Galluzzi L, Kroemer G. Metabolic control of cell death. Science. 2014;345:1466.CrossRef
41.
Lalaoui N, Lindqvist LM, Sandow JJ, Ekert PG. The molecular relationships between apoptosis, autophagy and necroptosis. Semin Cell Dev Biol. 2015;39:63–9.CrossRefPubMed
42.
Metadata
Title
MiR-20a-5p suppresses tumor proliferation by targeting autophagy-related gene 7 in neuroblastoma
Authors
Yongbo Yu
Jie Zhang
Yaqiong Jin
Yeran Yang
Jin Shi
Feng Chen
Shujing Han
Ping Chu
Jie Lu
Huanmin Wang
Yongli Guo
Xin Ni
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2018
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-017-0499-2

Other articles of this Issue 1/2018

Cancer Cell International 1/2018 Go to the issue

Primary Research

Allogeneic stem-cell transplantation for multiple myeloma: a systematic review and meta-analysis from 2007 to 2017

Primary research

Establishment and characterization of three stable Basal/HER2-positive breast cancer cell lines derived from Chinese breast carcinoma with identical missense mutations in the DNA-binding domain of TP53

Primary Research

Arachidonic acid-induced Ca2+ entry and migration in a neuroendocrine cancer cell line

Primary research

MicroRNA-218-5p inhibits cell growth and metastasis in cervical cancer via LYN/NF-κB signaling pathway

Primary Research

Effects of secreted frizzled-related protein 1 on proliferation, migration, invasion, and apoptosis of colorectal cancer cells

Primary Research

Epistructured catechins, EGCG and EC facilitate apoptosis induction through targeting de novo lipogenesis pathway in HepG2 cells
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