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
BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

The suppressive role of miR-542-5p in NSCLC: the evidence from clinical data and in vivo validation using a chick chorioallantoic membrane model

Authors: Rong-quan He, Xiao-jiao Li, Lu Liang, You Xie, Dian-zhong Luo, Jie Ma, Zhi-gang Peng, Xiao-hua Hu, Gang Chen

Published in: BMC Cancer | Issue 1/2017

Login to get access

Abstract

Background

Non-small cell lung cancer (NSCLC) has led to the highest cancer-related mortality for decades. To enhance the efficiency of early diagnosis and therapy, more efforts are urgently needed to reveal the origins of NSCLC. In this study, we explored the effect of miR-542-5p in NSCLC with clinical samples and in vivo models and further explored the prospective function of miR-542-5p though bioinformatics methods.

Methods

A total of 125 NSCLC tissue samples were collected, and the expression of miR-542-5p was detected by qRT-PCR. The relationship between miR-542-5p level and clinicopathological features was analyzed. The effect of miR-542-5p on survival time was also explored with K-M survival curves and Cox’s regression. The effect of miR-542-5p on the tumorigenesis of NSCLC was verified with a chick chorioallantoic membrane (CAM) model. The potential target genes were predicted by bioinformatics tools, and relevant pathways were analyzed by GO and KEGG. Several hub genes were validated by Proteinatlas.

Results

The expression of miR-542-5p was down-regulated in NSCLC tissues, and consistent results were also found in the subgroups of adenocarcinoma and squamous cell carcinoma. Down-regulation of miR-542-5p was found to be connected with advanced TNM stage, vascular invasion, lymphatic metastasis and EGFR. Survival analyses showed that patients with lower miR-542-5p levels had markedly poorer prognosis. Both tumor growth and angiogenesis were significantly suppressed by miR-542-5p mimic in the CAM model. The potential 457 target genes of miR-542-5p were enriched in several key cancer-related pathways, such as morphine addiction and the cAMP signaling pathway from KEGG. Interestingly, six genes (GABBR1, PDE4B, PDE4C, ADCY6, ADCY1 and GIPR) from the cAMP signaling pathway were confirmed to be overexpressed in NSCLCs tissues.

Conclusions

This evidence suggests that miR-542-5p is a potential tumor-suppressed miRNA in NSCLC, which has the potential to act as a diagnostic and therapeutic target of NSCLC.
Literature
1.
Martino EC, Misso G, Pastina P, Costantini S, Vanni F, Gandolfo C, Botta C, Capone F, Lombardi A, Pirtoli L, et al. Immune-modulating effects of bevacizumab in metastatic non-small-cell lung cancer patients. Cell Death Discov. 2016;2:16025.CrossRefPubMedPubMedCentral
2.
Lemjabbar-Alaoui H, Hassan OU, Yang YW, Buchanan P. Lung cancer: biology and treatment options. Biochim Biophys Acta. 2015;1856(2):189–210.PubMedPubMedCentral
3.
Zaporozhchenko IA, Morozkin ES, Skvortsova TE, Ponomaryova AA, Rykova EY, Cherdyntseva NV, Polovnikov ES, Pashkovskaya OA, Pokushalov EA, Vlassov VV, et al. Plasma miR-19b and miR-183 as potential biomarkers of lung cancer. PLoS One. 2016;11(10):e0165261.CrossRefPubMedPubMedCentral
4.
Wang D, Narula N, Azzopardi S, Smith RS, Nasar A, Altorki NK, Mittal V, Somwar R, Stiles BM, Du YN. Expression of the receptor for hyaluronic acid mediated motility (RHAMM) is associated with poor prognosis and metastasis in non-small cell lung carcinoma. Oncotarget. 2016;7(26):39957–69.CrossRefPubMedPubMedCentral
5.
6.
Cristobal I, Madoz-Gurpide J, Rojo F, Garcia-Foncillas J. Potential therapeutic value of miR-425-5p in metastatic colorectal cancer. J Cell Mol Med. 2016;20(11):2213–4.CrossRefPubMedPubMedCentral
7.
Lin CH, Tsai CH, Yeh CT, Liang JL, Hung WC, Lin FC, Chang WL, Li HY, Yao YC, Hsu TI, et al. MiR-193a-5p/ERBB2 act as concurrent chemoradiation therapy response indicator of esophageal squamous cell carcinoma. Oncotarget. 2016;7(26):39680–93.CrossRefPubMedPubMedCentral
8.
Leidinger P, Brefort T, Backes C, Krapp M, Galata V, Beier M, Kohlhaas J, Huwer H, Meese E, Keller A. High-throughput qRT-PCR validation of blood microRNAs in non-small cell lung cancer. Oncotarget. 2016;7(4):4611–23.CrossRefPubMed
9.
Molina-Pinelo S, Gutierrez G, Pastor MD, Hergueta M, Moreno-Bueno G, Garcia-Carbonero R, Nogal A, Suarez R, Salinas A, Pozo-Rodriguez F, et al. MicroRNA-dependent regulation of transcription in non-small cell lung cancer. PLoS One. 2014;9(3):e90524.CrossRefPubMedPubMedCentral
10.
Tang R, Liang L, Luo D, Feng Z, Huang Q, He R, Gan T, Yang L, Chen G. Downregulation of MiR-30a is associated with poor prognosis in lung cancer. Med Sci Monit. 2015;21:2514–20.CrossRefPubMedPubMedCentral
11.
Ren F, Ding H, Huang S, Wang H, Wu M, Luo D, Dang Y, Yang L, Chen G. Expression and clinicopathological significance of miR-193a-3p and its potential target astrocyte elevated gene-1 in non-small lung cancer tissues. Cancer Cell Int. 2015;15:80.CrossRefPubMedPubMedCentral
12.
Lan D, Zhang X, He R, Tang R, Li P, He Q, Chen G. MiR-133a is downregulated in non-small cell lung cancer: a study of clinical significance. Eur J Med Res. 2015;20:50.CrossRefPubMedPubMedCentral
13.
Chen G, Umelo IA, Lv S, Teugels E, Fostier K, Kronenberger P, Dewaele A, Sadones J, Geers C, De Greve J. miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells. PLoS One. 2013;8(3):e60317.CrossRefPubMedPubMedCentral
14.
Castilla MA, Moreno-Bueno G, Romero-Perez L, Van De Vijver K, Biscuola M, Lopez-Garcia MA, Prat J, Matias-Guiu X, Cano A, Oliva E, et al. Micro-RNA signature of the epithelial-mesenchymal transition in endometrial carcinosarcoma. J Pathol. 2011;223(1):72–80.CrossRefPubMed
15.
Bray I, Tivnan A, Bryan K, Foley NH, Watters KM, Tracey L, Davidoff AM, Stallings RL. MicroRNA-542-5p as a novel tumor suppressor in neuroblastoma. Cancer Lett. 2011;303(1):56–64.CrossRefPubMedPubMedCentral
16.
Gaedcke J, Grade M, Camps J, Sokilde R, Kaczkowski B, Schetter AJ, Difilippantonio MJ, Harris CC, Ghadimi BM, Moller S, et al. The rectal cancer microRNAome--microRNA expression in rectal cancer and matched normal mucosa. Clin Cancer Res. 2012;18(18):4919–30.CrossRefPubMed
17.
Cheng DD, Yu T, Hu T, Yao M, Fan CY, Yang QC. MiR-542-5p is a negative prognostic factor and promotes osteosarcoma tumorigenesis by targeting HUWE1. Oncotarget. 2015;6(40):42761–72.CrossRefPubMedPubMedCentral
18.
Yamaguchi G, Takanashi M, Tanaka M, Fujita K, Ohira T, Kuroda M, Ikeda N. Isolation of miRNAs that target EGFR mRNA in human lung cancer. Biochem Biophys Res Commun. 2012;420(2):411–6.CrossRefPubMed
19.
Rahamim Ben-Navi L, Almog T, Yao Z, Seger R, Naor Z. A-Kinase anchoring protein 4 (AKAP4) is an ERK1/2 substrate and a switch molecule between cAMP/PKA and PKC/ERK1/2 in human spermatozoa. Sci Rep. 2016;6:37922.CrossRefPubMedPubMedCentral
20.
Shaikh D, Zhou Q, Chen T, Ibe JC, Raj JU, Zhou G. cAMP-dependent protein kinase is essential for hypoxia-mediated epithelial-mesenchymal transition, migration, and invasion in lung cancer cells. Cell Signal. 2012;24(12):2396–406.CrossRefPubMed
21.
Jeong MJ, Kim EJ, Cho EA, Ye SK, Kang GH, Juhnn YS. cAMP signalling decreases p300 protein levels by promoting its ubiquitin/proteasome dependent degradation via Epac and p38 MAPK in lung cancer cells. FEBS Lett. 2013;587(9):1373–8.CrossRefPubMed
22.
23.
You B, Yang YL, Xu Z, Dai Y, Liu S, Mao JH, Tetsu O, Li H, Jablons DM, You L. Inhibition of ERK1/2 down-regulates the hippo/YAP signaling pathway in human NSCLC cells. Oncotarget. 2015;6(6):4357–68.CrossRefPubMedPubMedCentral
24.
Yuan Y, Zhong W, Ma G, Zhang B, Tian H. Yes-associated protein regulates the growth of human non-small cell lung cancer in response to matrix stiffness. Mol Med Rep. 2015;11(6):4267–72.CrossRefPubMed
25.
Zhao Z, Zheng N, Wang L, Hou Y, Zhou X, Wang Z. Rottlerin exhibits antitumor activity via down-regulation of TAZ in non-small cell lung cancer. Oncotarget. 2016; [Epub ahead of print]
26.
Zhang X, Liu X, Luo J, Xiao W, Ye X, Chen M, Li Y, Zhang GJ. Notch3 inhibits epithelial-mesenchymal transition by activating Kibra-mediated hippo/YAP signaling in breast cancer epithelial cells. Oncogene. 2016;5(11):e269.CrossRef
27.
Denlinger CE, Ikonomidis JS, Reed CE, Spinale FG. Epithelial to mesenchymal transition: the doorway to metastasis in human lung cancers. J Thorac Cardiovasc Surg. 2010;140(3):505–13.CrossRefPubMed
28.
Lim SK, Lu SY, Kang SA, Tan HJ, Li Z, Adrian Wee ZN, Guan JS, Reddy Chichili VP, Sivaraman J, Putti T, et al. Wnt Signaling promotes breast cancer by blocking ITCH-mediated degradation of YAP/TAZ transcriptional Coactivator WBP2. Cancer Res. 2016;76(21):6278–89.CrossRefPubMed
Metadata
Title
The suppressive role of miR-542-5p in NSCLC: the evidence from clinical data and in vivo validation using a chick chorioallantoic membrane model
Authors
Rong-quan He
Xiao-jiao Li
Lu Liang
You Xie
Dian-zhong Luo
Jie Ma
Zhi-gang Peng
Xiao-hua Hu
Gang Chen
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3646-1

Other articles of this Issue 1/2017

BMC Cancer 1/2017 Go to the issue

Research article

Effects of interactions between common genetic variants and smoking on colorectal cancer

Research article

Cost-effectiveness analysis of the introduction of S-1 therapy for first-line metastatic breast cancer treatment in Japan: results from the randomized phase III SELECT BC trial

Research article

Country and regional variations in purchase prices for essential cancer medications

Research article

Men’s perceptions of prostate cancer diagnosis and care: insights from qualitative interviews in Victoria, Australia

Research article

CpG promoter methylation of the ALKBH3 alkylation repair gene in breast cancer

Research article

New use of low-dose aspirin and risk of colorectal cancer by stage at diagnosis: a nested case–control study in UK general practice
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