Increased expression of microRNA-338-3p contributes to production of Dsg3 antibody in pemphigus vulgaris patients

Liu,Qingxiu; Cui,Feiyi; Wang,Menglei; Xiong,Hao; Peng,Xiaoming; Liang,Liuping; Li,Li; Zhang,Jing; Peng,Xuebiao; Zeng,Kang

doi:10.3892/mmr.2018.8934

July-2018 Volume 18 Issue 1

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

July-2018 Volume 18 Issue 1

Full Size Image

Article

Increased expression of microRNA-338-3p contributes to production of Dsg3 antibody in pemphigus vulgaris patients

Authors:
- Qingxiu Liu
- Feiyi Cui
- Menglei Wang
- Hao Xiong
- Xiaoming Peng
- Liuping Liang
- Li Li
- Jing Zhang
- Xuebiao Peng
- Kang Zeng
View Affiliations / Copyright

Affiliations: Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Medical Apparatus and Equipment Deployment, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Pages: 550-556
|
Published online on: April 26, 2018

https://doi.org/10.3892/mmr.2018.8934
Expand metrics +

Abstract

Expression of microRNA-338-3p (miR-338-3p) was aberrantly elevated in pemphigus vulgaris (PV), although its role in PV is still unknown. The present study investigated the functional role and possible molecular mechanisms of miR-338-3p in PV. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect miR-338-3p expression in peripheral blood mononuclear cells (PBMCs) from patients with PV. Correlation with disease severity and anti-desmoglein 3 antibody (anti-Dsg3) titers were analyzed in patients with PV. The effects of overexpression and knockdown of miR-338-3p expression in PBMCs and effects on Th1 and Th2 cytokines were also examined using ELISA. The luciferase reporter analysis, RT-qPCR and western blot analysis were applied to investigate potential and functional target genes. The data showed that miR-338-3p expression was significantly upregulated in PV and the upregulation of miR-338-3p associated with disease severity and a high anti-Dsg3 antibody titer. Expression of miR-338-3p/mimic in healthy PBMCs significantly downregulated Th1 cytokine (IFN-γ) and upregulated Th2 cytokines (IL-4 and IL-10), whereas knockdown of miR-338-3p expression in PBMCs from patients with PV induced the reverse effects. Overexpression of miR-338-3p suppressed cell viability. Luciferase reporter, RT-qPCR and western blot assays idnicated that TNFR1-associated death domain protein (TRADD) was the direct and functional target of miR-338-3p. Increased expression of miR-338-3p contributed to the production of Dsg3 antibody by inhibiting TRADD expression to induce an imbalance in Th1/Th2 cell functions. Taken together, this study suggests that miR-338-3p may be used as a potential therapeutic target for PV treatment.

View Figures

View References

1	Hertl M and Veldman C: T-cellular autoimmunity against desmogleins in pemphigus, an autoantibody-mediated bullous disorder of the skin. Autoimmun Rev. 2:278–283. 2003. View Article : Google Scholar : PubMed/NCBI
2	Rizzo C, Fotino M, Zhang Y, Chow S, Spizuoco A and Sinha AA: Direct characterization of human T cells in pemphigus vulgaris reveals elevated autoantigen-specific Th2 activity in association with active disease. Clin Exp Dermatol. 30:535–540. 2005. View Article : Google Scholar : PubMed/NCBI
3	Satyam A, Khandpur S, Sharma VK and Sharma A: Involvement of T(H)1/T(H)2 cytokines in the pathogenesis of autoimmune skin disease-Pemphigus vulgaris. Immunol Invest. 38:498–509. 2009. View Article : Google Scholar : PubMed/NCBI
4	Gandhi R: miRNA in multiple sclerosis: Search for novel biomarkers. Mult Scler. 21:1095–1103. 2015. View Article : Google Scholar : PubMed/NCBI
5	Stagakis E, Bertsias G, Verginis P, Nakou M, Hatziapostolou M, Kritikos H, Iliopoulos D and Boumpas DT: Identification of novel microRNA signatures linked to human lupus disease activity and pathogenesis: miR-21 regulates aberrant T cell responses through regulation of PDCD4 expression. Ann Rheum Dis. 70:1496–1506. 2011. View Article : Google Scholar : PubMed/NCBI
6	Churov AV, Oleinik EK and Knip M: MicroRNAs in rheumatoid arthritis: Altered expression and diagnostic potential. Autoimmun Rev. 14:1029–1037. 2015. View Article : Google Scholar : PubMed/NCBI
7	Langkilde A, Raaby L, Johansen C and Iversen L: MicroRNA normalization candidates for quantitative reverse-transcriptase polymerase chain reaction in real time in lesional and nonlesional psoriatic skin. Br J Dermatol. 169:677–681. 2013. View Article : Google Scholar : PubMed/NCBI
8	Wang M, Liang L, Li L, Han K, Li Q, Peng Y, Peng X and Zeng K: Increased miR-424-5p expression in peripheral blood mononuclear cells from patients with pemphigus. Mol Med Rep. 15:3479–3484. 2017. View Article : Google Scholar : PubMed/NCBI
9	Shan Y, Li X, You B, Shi S, Zhang Q and You Y: MicroRNA-338 inhibits migration and proliferation by targeting hypoxia-induced factor 1α in nasopharyngeal carcinoma. Oncol Rep. 34:1943–1952. 2015. View Article : Google Scholar : PubMed/NCBI
10	Sun J, Feng X, Gao S and Xiao Z: microRNA-338-3p functions as a tumor suppressor in human non-small-cell lung carcinoma and targets Ras-related protein 14. Mol Med Rep. 11:1400–1406. 2015. View Article : Google Scholar : PubMed/NCBI
11	Wang G and Sun Y, He Y, Ji C, Hu B and Sun Y: MicroRNA-338-3p inhibits cell proliferation in hepatocellular carcinoma by target forkhead box P4 (FOXP4). Int J Clin Exp Pathol. 8:337–344. 2015.PubMed/NCBI
12	Huang N, Wu Z, Lin L, Zhou M, Wang L, Ma H, Xia J, Bin J, Liao Y and Liao W: MiR-338-3p inhibits epithelial-mesenchymal transition in gastric cancer cells by targeting ZEB2 and MACC1/Met/Akt signaling. Oncotarget. 6:15222–15234. 2015.PubMed/NCBI
13	Jin Y, Zhao M, Xie Q, Zhang H, Wang Q and Ma Q: MicroRNA-338-3p functions as tumor suppressor in breast cancer by targeting SOX4. Int J Oncol. 47:1594–1602. 2015. View Article : Google Scholar : PubMed/NCBI
14	Li X, Li Z, Yang G and Pan Z: MicroRNA-338-3p suppresses tumor growth of esophageal squamous cell carcinoma in vitro and in vivo. Mol Med Rep. 12:3951–3957. 2015. View Article : Google Scholar : PubMed/NCBI
15	Tsuchiya S, Oku M, Imanaka Y, Kunimoto R, Okuno Y, Terasawa K, Sato F, Tsujimoto G and Shimizu K: MicroRNA-338-3p and microRNA-451 contribute to the formation of basolateral polarity in epithelial cells. Nucleic Acids Res. 37:3821–3827. 2009. View Article : Google Scholar : PubMed/NCBI
16	Sun Q, Liu H, Lin H, Yuan G, Zhang L and Chen Z: MicroRNA-338-3p promotes differentiation of mDPC6T into odontoblast-like cells by targeting Runx2. Mol Cell Biochem. 377:143–149. 2013. View Article : Google Scholar : PubMed/NCBI
17	Ebrahimi-Barough S, Massumi M, Kouchesfahani HM and Ai J: Derivation of pre-oligodendrocytes from human endometrial stromal cells using overexpression of microRNA 338. J Mol Neurosci. 51:337–343. 2013. View Article : Google Scholar : PubMed/NCBI
18	Magni S, Comani Buoli G, Elli L, Vanessi S, Ballarini E, Nicolini G, Rusconi M, Castoldi M, Meneveri R, Muckenthaler MU, et al: miRNAs affect the expression of innate and adaptive immunity proteins in celiac disease. Am J Gastroenterol. 109:1662–1674. 2014. View Article : Google Scholar : PubMed/NCBI
19	Pan M, Zhu H and Xu R: Immune cellular regulation on autoantibody production in pemphigus. J Dermatol. 42:11–17. 2015. View Article : Google Scholar : PubMed/NCBI
20	Pobezinskaya YL and Liu Z: The role of TRADD in death receptor signaling. Cell Cycle. 11:871–876. 2012. View Article : Google Scholar : PubMed/NCBI
21	Jin Z and El-Deiry WS: Distinct signaling pathways in TRAIL-versus tumor necrosis factor-induced apoptosis. Mol Cell Biol. 26:8136–8148. 2006. View Article : Google Scholar : PubMed/NCBI
22	Cao X, Pobezinskaya YL, Morgan MJ and Liu ZG: The role of TRADD in TRAIL-induced apoptosis and signaling. FASEB J. 25:1353–1358. 2011. View Article : Google Scholar : PubMed/NCBI
23	Micheau O and Tschopp J: Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell. 114:181–190. 2003. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Increased expression of microRNA-338-3p contributes to production of Dsg3 antibody in pemphigus vulgaris patients

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Related Articles