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MicroRNA-135b Regulates Leucine Zipper Tumor Suppressor 1 in Cutaneous Squamous Cell Carcinoma. PLoS One 2015;10(5):e0125412

Date

05/06/2015

Pubmed ID

25938461

Pubmed Central ID

PMC4418692

DOI

10.1371/journal.pone.0125412

Scopus ID

2-s2.0-84929084940   18 Citations

Abstract

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and it presents a therapeutic challenge in organ transplant recipient patients. Despite the need, there are only a few targeted drug treatment options. Recent studies have revealed a pivotal role played by microRNAs (miRNAs) in multiple cancers, but only a few studies tested their function in cSCC. Here, we analyzed differential expression of 88 cancer related miRNAs in 43 study participants with cSCC; 32 immunocompetent, 11 OTR patients, and 15 non-lesional skin samples by microarray analysis. Of the examined miRNAs, miR-135b was the most upregulated (13.3-fold, 21.5-fold; p=0.0001) in both patient groups. Similarly, the miR-135b expression was also upregulated in three cSCC cell lines when evaluated by quantitative real-time PCR. In functional studies, inhibition of miR-135b by specific anti-miR oligonucleotides resulted in upregulation of its target gene LZTS1 mRNA and protein levels and led to decreased cell motility and invasion of both primary and metastatic cSCC cell lines. In contrast, miR-135b overexpression by synthetic miR-135b mimic induced further down-regulation of LZTS1 mRNA in vitro and increased cancer cell motility and invasiveness. Immunohistochemical evaluation of 67 cSCC tumor tissues demonstrated that miR-135b expression inversely correlated with LZTS1 staining intensity and the tumor grade. These results indicate that miR-135b functions as an oncogene in cSCC and provide new understanding into its pathological role in cSCC progression and invasiveness.

Author List

Olasz EB, Seline LN, Schock AM, Duncan NE, Lopez A, Lazar J, Flister MJ, Lu Y, Liu P, Sokumbi O, Harwood CA, Proby CM, Neuburg M, Lazarova Z

Authors

Pengyuan Liu PhD Adjunct Professor in the Physiology department at Medical College of Wisconsin
Edit Olasz MD, PhD Associate Professor in the Dermatology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Carcinoma, Squamous Cell
Cell Line, Tumor
Cell Movement
Cell Proliferation
DNA-Binding Proteins
Down-Regulation
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
MicroRNAs
Neoplasm Invasiveness
Skin Neoplasms
Transfection
Tumor Suppressor Proteins
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d