MicroRNA-205-5p inhibits skin cancer cell proliferation and increase drug sensitivity by targeting TNFAIP8

Abstract Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is a member of the TIPE/TNFAIP8 family which regulates tumor growth and survival. Our goal is to delineate the detailed oncogenic role of TNFAIP8 in skin cancer development and progression. Here we demonstrated that higher expression of TN...

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Main Authors: Xinhong Ge, Suryakant Niture, Minghui Lin, Patrice Cagle, P. Andy Li, Deepak Kumar
Format: Article
Language:English
Published: Nature Publishing Group 2021-03-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-85097-6
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spelling doaj-710c00f389104119aaf99dc155064fa12021-03-11T12:20:34ZengNature Publishing GroupScientific Reports2045-23222021-03-0111111410.1038/s41598-021-85097-6MicroRNA-205-5p inhibits skin cancer cell proliferation and increase drug sensitivity by targeting TNFAIP8Xinhong Ge0Suryakant Niture1Minghui Lin2Patrice Cagle3P. Andy Li4Deepak Kumar5Department of Dermatology, General Hospital of Ningxia Medical UniversityJulius L. Chambers Biomedical Biotechnology Research Institute (BBRI), North Carolina Central UniversityDepartment of Respiratory Diseases, The Forth People’s Hospital of Ningxia Hui Autonomous RegionJulius L. Chambers Biomedical Biotechnology Research Institute (BBRI), North Carolina Central UniversityDepartment of Pharmaceutical Sciences, Bio-Manufacturing Research Institute and Technology Enterprise (BRITE), College of Health and Sciences, North Carolina Central UniversityJulius L. Chambers Biomedical Biotechnology Research Institute (BBRI), North Carolina Central UniversityAbstract Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is a member of the TIPE/TNFAIP8 family which regulates tumor growth and survival. Our goal is to delineate the detailed oncogenic role of TNFAIP8 in skin cancer development and progression. Here we demonstrated that higher expression of TNFAIP8 is associated with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma development in patient tissues. Induction of TNFAIP8 expression by TNFα or by ectopic expression of TNFAIP8 in SCC or melanoma cell lines resulted in increased cell growth/proliferation. Conversely, silencing of TNFAIP8 decreased cell survival/cell migration in skin cancer cells. We also showed that miR-205-5p targets the 3′UTR of TNFAIP8 and inhibits TNFAIP8 expression. Moreover, miR-205-5p downregulates TNFAIP8 mediated cellular autophagy, increased sensitivity towards the B-RAFV600E mutant kinase inhibitor vemurafenib, and induced cell apoptosis in melanoma cells. Collectively our data indicate that miR-205-5p acts as a tumor suppressor in skin cancer by targeting TNFAIP8.https://doi.org/10.1038/s41598-021-85097-6
collection DOAJ
language English
format Article
sources DOAJ
author Xinhong Ge
Suryakant Niture
Minghui Lin
Patrice Cagle
P. Andy Li
Deepak Kumar
spellingShingle Xinhong Ge
Suryakant Niture
Minghui Lin
Patrice Cagle
P. Andy Li
Deepak Kumar
MicroRNA-205-5p inhibits skin cancer cell proliferation and increase drug sensitivity by targeting TNFAIP8
Scientific Reports
author_facet Xinhong Ge
Suryakant Niture
Minghui Lin
Patrice Cagle
P. Andy Li
Deepak Kumar
author_sort Xinhong Ge
title MicroRNA-205-5p inhibits skin cancer cell proliferation and increase drug sensitivity by targeting TNFAIP8
title_short MicroRNA-205-5p inhibits skin cancer cell proliferation and increase drug sensitivity by targeting TNFAIP8
title_full MicroRNA-205-5p inhibits skin cancer cell proliferation and increase drug sensitivity by targeting TNFAIP8
title_fullStr MicroRNA-205-5p inhibits skin cancer cell proliferation and increase drug sensitivity by targeting TNFAIP8
title_full_unstemmed MicroRNA-205-5p inhibits skin cancer cell proliferation and increase drug sensitivity by targeting TNFAIP8
title_sort microrna-205-5p inhibits skin cancer cell proliferation and increase drug sensitivity by targeting tnfaip8
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2021-03-01
description Abstract Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is a member of the TIPE/TNFAIP8 family which regulates tumor growth and survival. Our goal is to delineate the detailed oncogenic role of TNFAIP8 in skin cancer development and progression. Here we demonstrated that higher expression of TNFAIP8 is associated with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma development in patient tissues. Induction of TNFAIP8 expression by TNFα or by ectopic expression of TNFAIP8 in SCC or melanoma cell lines resulted in increased cell growth/proliferation. Conversely, silencing of TNFAIP8 decreased cell survival/cell migration in skin cancer cells. We also showed that miR-205-5p targets the 3′UTR of TNFAIP8 and inhibits TNFAIP8 expression. Moreover, miR-205-5p downregulates TNFAIP8 mediated cellular autophagy, increased sensitivity towards the B-RAFV600E mutant kinase inhibitor vemurafenib, and induced cell apoptosis in melanoma cells. Collectively our data indicate that miR-205-5p acts as a tumor suppressor in skin cancer by targeting TNFAIP8.
url https://doi.org/10.1038/s41598-021-85097-6
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