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
Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

Open Access 01-12-2022 | Gastric Cancer | Research

hsa-miR-875-5p inhibits tumorigenesis and suppresses TGF-β signalling by targeting USF2 in gastric cancer

Authors: Shenshuo Gao, Zhikai Zhang, Xubin Wang, Yan Ma, Chensheng Li, Hongjun Liu, Changqing Jing, Leping Li, Xiaobo Guo

Published in: Journal of Translational Medicine | Issue 1/2022

Login to get access

Abstract

Background

Gastric cancer (GC) is one of the most common malignancies, and an increasing number of studies have shown that its pathogenesis is regulated by various miRNAs. In this study, we investigated the role of miR-875-5p in GC.

Methods

The expression of miR-875-5p was detected in human GC specimens and cell lines by miRNA qRT–PCR. The effect of miR-875-5p on GC proliferation was determined by Cell Counting Kit-8 (CCK-8) proliferation and 5-ethynyl-2′-deoxyuridine (EdU) assays. Migration and invasion were examined by transwell migration and invasion assays as well as wound healing assays. The interaction between miR-875-5p and its target gene upstream stimulatory factor 2(USF2) was verified by dual luciferase reporter assays. The effects of miR-875-5p in vivo were studied in xenograft nude mouse models. Related proteins were detected by western blot.

Results

The results showed that miR-875-5p inhibited the proliferation, migration and invasion of GC cells in vitro and inhibited tumorigenesis in vivo. USF2 was proved to be a direct target of miR-875-5p. Knockdown of USF2 partially counteracted the effects of miR-875-5p inhibitor. Overexpression of miR-875-5p could inhibit proliferation, migration and invasion and suppress the TGF-β signalling pathway by downregulating USF2.

Conclusions

MiR-875-5p can inhibit the progression of GC by directly targeting USF2. And in the future, miR-875-5p is expected to be a potential target for GC diagnosis and treatment.
Literature
1.
2.
Cao W, Chen HD, Yu YW, Li N, Chen WQ. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J (Engl). 2021;134:783–91.
3.
4.
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.PubMed
5.
Pu M, Chen J, Tao Z, Miao L, Qi X, Wang Y, Ren J. Regulatory network of miRNA on its target: coordination between transcriptional and post-transcriptional regulation of gene expression. Cell Mol Life Sci. 2019;76:441–51.PubMed
6.
Zhang N, Hu G, Myers TG, Williamson PR. Protocols for the analysis of microRNA expression, biogenesis, and function in immune cells. Curr Protoc Immunol. 2019;126: e78.PubMedPubMedCentral
7.
Bhaskaran M, Mohan M. MicroRNAs: history, biogenesis, and their evolving role in animal development and disease. Vet Pathol. 2014;51:759–74.PubMed
8.
Saliminejad K, Khorram Khorshid HR, Soleymani Fard S, Ghaffari SH. An overview of microRNAs: biology, functions, therapeutics, and analysis methods. J Cell Physiol. 2019;234:5451–65.PubMed
9.
Zendjabil M, Favard S, Tse C, Abbou O, Hainque B. The microRNAs as biomarkers: what prospects? C R Biol. 2017;340:114–31.PubMed
10.
Zamanian Azodi M, Rezaei-Tavirani M, Rezaei-Tavirani M, Robati RM. Gestational diabetes mellitus regulatory network identifies hsa-miR-145–5p and hsa-miR-875–5p as potential biomarkers. Int J Endocrinol Metab. 2019;17: e86640.PubMedPubMedCentral
11.
Ye L, Yu Y, Zhao Y. Icariin-induced miR-875-5p attenuates epithelial-mesenchymal transition by targeting hedgehog signaling in liver fibrosis. J Gastroenterol Hepatol. 2020;35:482–91.PubMed
12.
Wang J, Lu Y, Ding H, Gu T, Gong C, Sun J, Zhang Z, Zhao Y, Ma C. The miR-875-5p inhibits SATB2 to promote the invasion of lung cancer cells. Gene. 2018;644:13–9.PubMed
13.
Kang N, Ou Y, Wang G, Chen J, Li D, Zhan Q. miR-875–5p exerts tumor-promoting function via down-regulation of CAPZA1 in esophageal squamous cell carcinoma. PeerJ. 2021;9: e10020.PubMedPubMedCentral
14.
Chen T, Sun L, Yao B, Wang L, Wang Y, Niu Y, Liu R, Mo H, Liu Z, Tu K, Liu Q. MicroRNA-875-5p inhibits tumor growth and metastasis of hepatocellular carcinoma by targeting eukaryotic translation initiation factor 3 subunit a. Oncol Rep. 2020;44:2067–79.PubMedPubMedCentral
15.
El Bezawy R, Cominetti D, Fenderico N, Zuco V, Beretta GL, Dugo M, Arrighetti N, Stucchi C, Rancati T, Valdagni R, et al. miR-875-5p counteracts epithelial-to-mesenchymal transition and enhances radiation response in prostate cancer through repression of the EGFR-ZEB1 axis. Cancer Lett. 2017;395:53–62.PubMed
16.
Zhang T, Cai X, Li Q, Xue P, Chen Z, Dong X, Xue Y. Hsa-miR-875-5p exerts tumor suppressor function through down-regulation of EGFR in colorectal carcinoma (CRC). Oncotarget. 2016;7:42225–40.PubMedPubMedCentral
17.
Tang Y, Meng X, Yu X, Shang H, Chen S, Liao L, Dong J. Inhibition of microRNA-875-5p promotes radioiodine uptake in poorly differentiated thyroid carcinoma cells by upregulating sodium-iodide symporter. J Endocrinol Invest. 2020;43:439–50.PubMed
18.
Yang Z, Zhi Q, Wang D, Zhang L, Preston B, Brandon C, Kuang Y, Miao R, Shi Y, Guo X. Long noncoding RNA C21orF96 promotes the migration, invasion and lymph node metastasis in gastric cancer. Anticancer Agents Med Chem. 2016;16:1101–8.PubMed
19.
Carthew RW, Chodosh LA, Sharp PA. An RNA polymerase II transcription factor binds to an upstream element in the adenovirus major late promoter. Cell. 1985;43:439–48.PubMed
20.
Miyamoto NG, Moncollin V, Egly JM, Chambon P. Specific interaction between a transcription factor and the upstream element of the adenovirus-2 major late promoter. Embo J. 1985;4:3563–70.PubMedPubMedCentral
21.
Sawadogo M, Van Dyke MW, Gregor PD, Roeder RG. Multiple forms of the human gene-specific transcription factor USF. I. Complete purification and identification of USF from HeLa cell nuclei. J Biol Chem. 1988;263:11985–93.PubMed
22.
Gregor PD, Sawadogo M, Roeder RG. The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer. Genes Dev. 1990;4:1730–40.PubMed
23.
Sirito M, Lin Q, Deng JM, Behringer RR, Sawadogo M. Overlapping roles and asymmetrical cross-regulation of the USF proteins in mice. Proc Natl Acad Sci USA. 1998;95:3758–63.PubMedPubMedCentral
24.
Yago M, Ohki R, Hatakeyama S, Fujita T, Ishikawa F. Variant forms of upstream stimulatory factors (USFs) control the promoter activity of hTERT, the human gene encoding the catalytic subunit of telomerase. FEBS Lett. 2002;520:40–6.PubMed
25.
Yan S, Sloane BF. Isolation of a novel USF2 isoform: repressor of cathepsin B expression. Gene. 2004;337:199–206.PubMed
26.
Sirito M, Lin Q, Maity T, Sawadogo M. Ubiquitous expression of the 43- and 44-kDa forms of transcription factor USF in mammalian cells. Nucleic Acids Res. 1994;22:427–33.PubMedPubMedCentral
27.
Roth U, Jungermann K, Kietzmann T. Modulation of glucokinase expression by hypoxia-inducible factor 1 and upstream stimulatory factor 2 in primary rat hepatocytes. Biol Chem. 2004;385:239–47.PubMed
28.
Bruno MEC, West RB, Schneeman TA, Bresnick EH, Kaetzel CS. Upstream stimulatory factor but not c-Myc enhances transcription of the human polymeric immunoglobulin receptor gene. Mol Immunol. 2004;40:695–708.PubMed
29.
Ocejo-Garcia M, Baokbah TA, Ashurst HL, Cowlishaw D, Soomro I, Coulson JM, Woll PJ. Roles for USF-2 in lung cancer proliferation and bronchial carcinogenesis. J Pathol. 2005;206:151–9.PubMed
30.
Tan Y, Chen Y, Du M, Peng Z, Xie P. USF2 inhibits the transcriptional activity of Smurf1 and Smurf2 to promote breast cancer tumorigenesis. Cell Signal. 2019;53:49–58.PubMed
31.
32.
Christensen LL, Tobiasen H, Holm A, Schepeler T, Ostenfeld MS, Thorsen K, Rasmussen MH, Birkenkamp-Demtroeder K, Sieber OM, Gibbs P, et al. MiRNA-362-3p induces cell cycle arrest through targeting of E2F1, USF2 and PTPN1 and is associated with recurrence of colorectal cancer. Int J Cancer. 2013;133:67–78.PubMed
33.
Deng M, Zeng C, Lu X, He X, Zhang R, Qiu Q, Zheng G, Jia X, Liu H, He Z. miR-218 suppresses gastric cancer cell cycle progression through the CDK6/Cyclin D1/E2F1 axis in a feedback loop. Cancer Lett. 2017;403:175–85.PubMed
34.
Shi Q, Li Y, Li S, Jin L, Lai H, Wu Y, Cai Z, Zhu M, Li Q, Li Y, et al. LncRNA DILA1 inhibits Cyclin D1 degradation and contributes to tamoxifen resistance in breast cancer. Nat Commun. 2020;11:5513.PubMedPubMedCentral
35.
Zhou S, Sun Q, Zhang H, Lian G, Liu H, Li L, Guo X. LncRNA C21orF96 promotes the invasion and metastasis of gastric cancer by regulating the expression of miR-875-5p and USF2 genes (in Chinese). Chin J Gen Surg. 2020;35:57–60.
36.
37.
Kwan JY, Psarianos P, Bruce JP, Yip KW, Liu FF. The complexity of microRNAs in human cancer. J Radiat Res. 2016;57(Suppl 1):i106–11.PubMedPubMedCentral
38.
Tong F, Cao P, Yin Y, Xia S, Lai R, Liu S. MicroRNAs in gastric cancer: from benchtop to bedside. Dig Dis Sci. 2014;59:24–30.PubMed
39.
Hayes J, Peruzzi PP, Lawler S. MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol Med. 2014;20:460–9.PubMed
40.
Bertoli G, Cava C, Castiglioni I. MicroRNAs: new biomarkers for diagnosis, prognosis, therapy prediction and therapeutic tools for breast cancer. Theranostics. 2015;5:1122–43.PubMedPubMedCentral
41.
Xing X, Du X, Lu Z, Ning T, Su X, Ke Y. Characterization of the promoter of 1A6/DRIM, a novel cancer-related gene and identification of its transcriptional activator. Gene. 2005;344:161–9.PubMed
42.
Horbach T, Gotz C, Kietzmann T, Dimova EY. Protein kinases as switches for the function of upstream stimulatory factors: implications for tissue injury and cancer. Front Pharmacol. 2015;6:3.PubMedPubMedCentral
43.
Choe C, Chen N, Sawadogo M. Decreased tumorigenicity of c-Myc-transformed fibroblasts expressing active USF2. Exp Cell Res. 2005;302:1–10.PubMed
44.
Chen N, Szentirmay MN, Pawar SA, Sirito M, Wang J, Wang Z, Zhai Q, Yang HX, Peehl DM, Ware JL, Sawadogo M. Tumor-suppression function of transcription factor USF2 in prostate carcinogenesis. Oncogene. 2006;25:579–87.PubMed
45.
Xie F, Ling L, van Dam H, Zhou F, Zhang L. TGF-β signaling in cancer metastasis. Acta Biochim Biophys Sin (Shanghai). 2018;50:121–32.
46.
Syed V. TGF-β signaling in cancer. J Cell Biochem. 2016;117:1279–87.PubMed
47.
48.
Li Q, Yue W, Li M, Jiang Z, Hou Z, Liu W, Ma N, Gan W, Li Y, Zhou T, et al. Downregulating long non-coding RNAs CTBP1-AS2 inhibits colorectal cancer development by modulating the miR-93–5p/TGF-beta/SMAD2/3 pathway. Front Oncol. 2021;11: 626620.PubMedPubMedCentral
Metadata
Title
hsa-miR-875-5p inhibits tumorigenesis and suppresses TGF-β signalling by targeting USF2 in gastric cancer
Authors
Shenshuo Gao
Zhikai Zhang
Xubin Wang
Yan Ma
Chensheng Li
Hongjun Liu
Changqing Jing
Leping Li
Xiaobo Guo
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03253-6

Other articles of this Issue 1/2022

Journal of Translational Medicine 1/2022 Go to the issue

Meeting report

Perspectives in Melanoma: meeting report from the Melanoma Bridge (December 2nd – 4th, 2021, Italy)

Review

Non-coding RNAs in lung cancer: emerging regulators of angiogenesis

Research

Spatial transcriptomics atlas reveals the crosstalk between cancer-associated fibroblasts and tumor microenvironment components in colorectal cancer

Research

miR-1297 sensitizes glioma cells to temozolomide (TMZ) treatment through targeting adrenomedullin (ADM)

Research

Lkb1 aggravates diffuse large B-cell lymphoma by promoting the function of Treg cells and immune escape

Research

VLCKD: a real time safety study in obesity
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits