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

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2020

01-12-2020 | Neuroblastoma | Primary research

SNHG16 promotes tumorigenesis and cisplatin resistance by regulating miR-338-3p/PLK4 pathway in neuroblastoma cells

Authors: Zhaoying Xu, Yongfa Sun, Danfeng Wang, Huifang Sun, Xiaojun Liu

Published in: Cancer Cell International | Issue 1/2020

Login to get access

Abstract

Background

Long noncoding RNA small nucleolar RNA host gene 16 (lncRNA SNHG16) has been revealed to be involved in the tumorigenesis of neuroblastoma. However, the role of SNHG16 in regulating cisplatin sensitivity in neuroblastoma remains largely unknown.

Methods

The expression of SNHG16, microRNA (miR)-338-3p and polo-like kinase 4 (PLK4) mRNA was measured using quantitative real-time polymerase chain reaction. The protein levels of PLK4, multidrug resistance protein 1 (MRP1), multidrug-resistance gene 1-type p-glycoprotein (P-gp) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related proteins were detected by Western blot. The half maximal inhibitory concentration (IC50) value, cell proliferation, migration and invasion were analyzed using Cell Counting Kit-8 assays or Transwell assay. Apoptotic cells were measured by Flow cytometry. The interaction between miR-338-3p and SNHG16 or PLK4 was confirmed by dual-luciferase reporter and RNA immunoprecipitation assay. In vivo experiments were conducted through the murine xenograft model.

Results

SNHG16 was up-regulated, while miR-338-3p was down-regulated in cisplatin-resistant neuroblastoma tissues and cells. SNHG16 silencing weakened cisplatin resistance, reflected by the reduction of IC50 value, down-regulation of MRP-1 and P-gp protein expression, suppression of proliferation, migration and invasion, as well as enhancement of apoptosis in SNHG16 deletion cisplatin-resistant neuroblastoma cells. Besides that, SNHG16 could regulate PLK4 expression by sponging miR-338-3p and SNHG16/miR-338-3p/PLK4 axis could affect the activation of PI3K/AKT pathway in cisplatin-resistant neuroblastoma cells. MiR-338-3p inhibition attenuated SNHG16 deletion-mediated impairment on cisplatin resistance and PLK4 overexpression reversed the decrease of cisplatin-resistance induced by miR-338-3p re-expression. Furthermore, SNHG16 knockdown contributed to the anti-tumor effect of cisplatin in neuroblastoma in vivo.

Conclusion

SNHG16 contributed to the tumorigenesis and cisplatin resistance in neuroblastoma possibly through miR-338-3p/PLK4 pathway, indicating a novel insight for overcoming chemoresistance in neuroblastoma patients.
Appendix
Available only for authorised users
Literature
1.
Sharp SE, Gelfand MJ, Shulkin BL. Pediatrics: diagnosis of neuroblastoma. Semin Nucl Med. 2011;41(5):345–53.PubMedCrossRef
2.
Irwin MS, Park JR. Neuroblastoma: paradigm for precision medicine. Pediatr Clin North Am. 2015;62(1):225–56.PubMedCrossRef
3.
Braekeveldt N, Bexell D. Patient-derived xenografts as preclinical neuroblastoma models. Cell Tissue Res. 2018;372(2):233–43.PubMedCrossRef
4.
Tsubota S, Kadomatsu K. Origin and initiation mechanisms of neuroblastoma. Cell Tissue Res. 2018;372(2):211–21.PubMedCrossRef
5.
6.
7.
Xu Y, Zhang X, Hu X, Zhou W, Zhang P, Zhang J, Yang S, Liu Y. The effects of lncRNA MALAT1 on proliferation, invasion and migration in colorectal cancer through regulating SOX9. Mol Med. 2018;24(1):52.PubMedPubMedCentralCrossRef
8.
Lei H, Gao Y, Xu X. LncRNA TUG1 influences papillary thyroid cancer cell proliferation, migration and EMT formation through targeting miR-145. Acta Biochim Biophys Sin (Shanghai). 2017;49(7):588–97.CrossRef
9.
Xiao J, Lv Y, Jin F, Liu Y, Ma Y, Xiong Y, Liu L, Zhang S, Sun Y, Tipoe GL, et al. LncRNA HANR promotes tumorigenesis and increase of chemoresistance in hepatocellular carcinoma. Cell Physiol Biochem. 2017;43(5):1926–38.PubMedCrossRef
10.
Cai C, Huo Q, Wang X, Chen B, Yang Q. SNHG16 contributes to breast cancer cell migration by competitively binding miR-98 with E2F5. Biochem Biophys Res Commun. 2017;485(2):272–8.PubMedCrossRef
11.
Lian D, Amin B, Du D, Yan W. Enhanced expression of the long non-coding RNA SNHG16 contributes to gastric cancer progression and metastasis. Cancer Biomark. 2017;21(1):151–60.PubMedCrossRef
12.
Liu Y, Gu S, Li H, Wang J, Wei C, Liu Q. SNHG16 promotes osteosarcoma progression and enhances cisplatin resistance by sponging miR-16 to upregulate ATG4B expression. Biochem Biophys Res Commun. 2019;518(1):127–33.PubMedCrossRef
13.
Guo Z, Zhang J, Fan L, Liu J, Yu H, Li X, Sun G. Long noncoding RNA (lncRNA) small nucleolar RNA host gene 16 (SNHG16) predicts poor prognosis and sorafenib resistance in hepatocellular carcinoma. Med Sci Monit. 2019;25:2079–86.PubMedPubMedCentralCrossRef
14.
Yu Y, Chen F, Yang Y, Jin Y, Shi J, Han S, Chu P, Lu J, Tai J, Wang S, et al. lncRNA SNHG16 is associated with proliferation and poor prognosis of pediatric neuroblastoma. Int J Oncol. 2019;55(1):93–102.PubMedPubMedCentral
15.
16.
Xia HL, Lv Y, Xu CW, Fu MC, Zhang T, Yan XM, Dai S, Xiong QW, Zhou Y, Wang J, et al. MiR-513c suppresses neuroblastoma cell migration, invasion, and proliferation through direct targeting glutaminase (GLS). Cancer Biomark. 2017;20(4):589–96.PubMedCrossRef
17.
Sharif S, Ghahremani MH, Soleimani M. Induction of morphological and functional differentiation of human neuroblastoma cells by miR-124. J Biosci. 2017;42(4):555–63.PubMedCrossRef
18.
Li D, Cao Y, Li J, Xu J, Liu Q, Sun X. miR-506 suppresses neuroblastoma metastasis by targeting ROCK1. Oncol Lett. 2017;13(1):417–22.PubMedCrossRef
19.
Chen JS, Liang LL, Xu HX, Chen F, Shen SL, Chen W, Chen LZ, Su Q, Zhang LJ, Bi J, et al. miR-338-3p inhibits epithelial-mesenchymal transition and metastasis in hepatocellular carcinoma cells. Oncotarget. 2017;8(42):71418–29.PubMedCrossRef
20.
Zhang P, Shao G, Lin X, Liu Y, Yang Z. MiR-338-3p inhibits the growth and invasion of non-small cell lung cancer cells by targeting IRS2. Am J Cancer Res. 2017;7(1):53–63.PubMedPubMedCentral
21.
Zhang X, Wang C, Li H, Niu X, Liu X, Pei D, Guo X, Xu X, Li Y. miR-338-3p inhibits the invasion of renal cell carcinoma by downregulation of ALK5. Oncotarget. 2017;8(38):64106–13.PubMedPubMedCentralCrossRef
22.
Chen X, Pan M, Han L, Lu H, Hao X, Dong Q. miR-338-3p suppresses neuroblastoma proliferation, invasion and migration through targeting PREX2a. FEBS Lett. 2013;587(22):3729–37.PubMedCrossRef
23.
Maniswami RR, Prashanth S, Karanth AV, Koushik S, Govindaraj H, Mullangi R, Rajagopal S, Jegatheesan SK. PLK4: a link between centriole biogenesis and cancer. Expert Opin Ther Targets. 2018;22(1):59–73.PubMedCrossRef
24.
Bailey AW, Suri A, Chou PM, Pundy T, Gadd S, Raimondi SL, Tomita T, Sredni ST. Polo-like kinase 4 (PLK4) is overexpressed in central nervous system neuroblastoma (CNS-NB). Bioengineering. 2018;5(4):E96.PubMedCrossRef
25.
De Bernardi B, Carli M, Casale F, Corciulo P, Cordero di Montezemolo L, De Laurentis C, Bagnulo S, Brisigotti M, Marchese N, Garaventa A, et al. Standard-dose and high-dose peptichemio and cisplatin in children with disseminated poor-risk neuroblastoma: two studies by the Italian Cooperative Group for Neuroblastoma. J Clin Oncol. 1992;10(12):1870–8.PubMedCrossRef
26.
Vella S, Penna I, Longo L, Pioggia G, Garbati P, Florio T, Rossi F, Pagano A. Perhexiline maleate enhances antitumor efficacy of cisplatin in neuroblastoma by inducing over-expression of NDM29 ncRNA. Sci Rep. 2015;5:18144.PubMedPubMedCentralCrossRef
27.
Ryan J, Tivnan A, Fay J, Bryan K, Meehan M, Creevey L, Lynch J, Bray IM, O’Meara A, Tracey L, et al. MicroRNA-204 increases sensitivity of neuroblastoma cells to cisplatin and is associated with a favourable clinical outcome. Br J Cancer. 2012;107(6):967–76.PubMedPubMedCentralCrossRef
28.
Sun W, Zu Y, Fu X, Deng Y. Knockdown of lncRNA-XIST enhances the chemosensitivity of NSCLC cells via suppression of autophagy. Oncol Rep. 2017;38(6):3347–54.PubMedPubMedCentral
29.
30.
Li S, Peng F, Ning Y, Jiang P, Peng J, Ding X, Zhang J, Jiang T, Xiang S. SNHG16 as the miRNA let-7b-5p sponge facilitates the G2/M and epithelial-mesenchymal transition by regulating CDC25B and HMGA2 expression in hepatocellular carcinoma. J Cell Biochem. 2020;121(3):2543–58.PubMedCrossRef
31.
32.
33.
Ergun S, Oztuzcu S. Oncocers: ceRNA-mediated cross-talk by sponging miRNAs in oncogenic pathways. Tumour Biol. 2015;36(5):3129–36.PubMedCrossRef
34.
Han J, Li J, Tang K, Zhang H, Guo B, Hou N, Huang C. miR-338-3p confers 5-fluorouracil resistance in p53 mutant colon cancer cells by targeting the mammalian target of rapamycin. Exp Cell Res. 2017;360(2):328–36.PubMedCrossRef
35.
Xu H, Zhao L, Fang Q, Sun J, Zhang S, Zhan C, Liu S, Zhang Y. MiR-338-3p inhibits hepatocarcinoma cells and sensitizes these cells to sorafenib by targeting hypoxia-induced factor 1alpha. PLoS ONE. 2014;9(12):e115565.PubMedPubMedCentralCrossRef
36.
Marina M, Saavedra HI. Nek2 and Plk4: prognostic markers, drivers of breast tumorigenesis and drug resistance. Front Biosci. 2014;19:352–65.CrossRef
37.
Wang J, Zuo J, Wang M, Ma X, Gao K, Bai X, Wang N, Xie W, Liu H. Pololike kinase 4 promotes tumorigenesis and induces resistance to radiotherapy in glioblastoma. Oncol Rep. 2019;41(4):2159–67.PubMedPubMedCentral
38.
Fianco G, Mongiardi MP, Levi A, De Luca T, Desideri M, Trisciuoglio D, Del Bufalo D, Cina I, Di Benedetto A, Mottolese M, et al. Caspase-8 contributes to angiogenesis and chemotherapy resistance in glioblastoma. eLife. 2017;6:e22593.PubMedPubMedCentralCrossRef
39.
Wu L, Bernal GM, Cahill KE, Pytel P, Fitzpatrick CA, Mashek H, Weichselbaum RR, Yamini B. BCL3 expression promotes resistance to alkylating chemotherapy in gliomas. Sci Transl Med. 2018;10(448):eaar2238.PubMedPubMedCentralCrossRef
40.
Zhang Z, Wang Z, Huang K, Liu Y, Wei C, Zhou J, Zhang W, Wang Q, Liang H, Zhang A, et al. PLK4 is a determinant of temozolomide sensitivity through phosphorylation of IKBKE in glioblastoma. Cancer Lett. 2019;443:91–107.PubMedCrossRef
41.
Li Z, Dai K, Wang C, Song Y, Gu F, Liu F, Fu L. Expression of polo-like kinase 4(PLK4) in breast cancer and its response to taxane-based neoadjuvant chemotherapy. J Cancer. 2016;7(9):1125–32.PubMedPubMedCentralCrossRef
42.
Martin-Orozco RM, Almaraz-Pro C, Rodriguez-Ubreva FJ, Cortes MA, Ropero S, Colomer R, Lopez-Ruiz P, Colas B. EGF prevents the neuroendocrine differentiation of LNCaP cells induced by serum deprivation: the modulator role of PI3K/Akt. Neoplasia. 2007;9(8):614–24.PubMedPubMedCentralCrossRef
43.
Fresno Vara JA, Casado E, de Castro J, Cejas P, Belda-Iniesta C, Gonzalez-Baron M. PI3K/Akt signalling pathway and cancer. Cancer Treat Rev. 2004;30(2):193–204.PubMedCrossRef
Metadata
Title
SNHG16 promotes tumorigenesis and cisplatin resistance by regulating miR-338-3p/PLK4 pathway in neuroblastoma cells
Authors
Zhaoying Xu
Yongfa Sun
Danfeng Wang
Huifang Sun
Xiaojun Liu
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01291-y

Other articles of this Issue 1/2020

Cancer Cell International 1/2020 Go to the issue

Correction

Correction to: Identification of prognosis-related genes and construction of multi-regulatory networks in pancreatic cancer microenvironment by bioinformatics analysis

Primary research

Musashi-1 promotes cancer stem cell properties of glioblastoma cells via upregulation of YTHDF1

Primary research

TNFAIP8 variants as potential epidemiological and predictive biomarkers in ovarian cancer

Primary research

Lonidamine potentiates the oncolytic efficiency of M1 virus independent of hexokinase 2 but via inhibition of antiviral immunity

Primary research

A novel risk score system of immune genes associated with prognosis in endometrial cancer

Primary research

CTLA4 has a profound impact on the landscape of tumor-infiltrating lymphocytes with a high prognosis value in clear cell renal cell carcinoma (ccRCC)
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