MiR-365 Promotes Cutaneous Squamous Cell Carcinoma (CSCC) through Targeting Nuclear Factor I/B (NFIB)

Meijuan Zhou,Zhenhua Ding,Liang Zhou,Li Zheng,Ling Guo,Hongxia Liu,Yinghui Wang,Chengshan Ou,Baohong Zhang

doi:10.1371/journal.pone.0100620

Meijuan Zhou, Zhenhua Ding + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0100620

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Journal: PloS one	Publication Date: Jun 20, 2014
Citations: 67	License type: CC BY 4.0

Affiliation: Southern Medical University

Abstract

Aberrant expression of microRNAs plays vital roles in tumor development and progression. As transcription factors (TFs) are the critical components of signaling cascades, specific targeting effects of microRNAs to specific TFs may determine the role of microRNAs in different cancers. In this study, we identified Nuclear Factor I/B (NFIB) as one of the targets of miR-365 which was previously verified as an onco-miR in cutaneous squamous cell carcinoma (CSCC). Down-regulation of NFIB was a general feature in both CSCC cell lines and tumors from patients which show drastically up-regulated miR-365 expression levels. The siRNA-based knockdown of NFIB mimic the carcinogenic transformation of normal cells by ectopically expression of miR-365 which indicates depletion of NFIB is necessary for miR-365 to exert its pro-carcinogenic function. NFIB may represent a functional barrier targeted by miR-365 to the development of CSCC. Further studies also discovered a conserved feedback regulatory circuitry formed by NFIB and miR-365 in CSCC development which may be potentially utilized as therapeutic target to improve the clinical CSCC treatment.

Highlights

Cutaneous squamous cell carcinoma counts about twenty percent of total skin cancers which is more malignant than basal cell cancers because cutaneous squamous cell carcinoma (CSCC) tend to grow and spread much faster than the later
Nuclear Factor I/B (NFIB) is Predicted to be the Direct Target of miR-365 As higher expression of miR-365 in CSCC tumors and cells has been verified in the previous study [7], the direct downstream targets of miR-365 become more important for understanding the oncogenic roles performed by miR-365
Development and progression, we began by examining the expression levels of NFIB in CSCC cell lines, A431, HSC-1 and Tca8113, which were compared with normal control (NC), HaCaT cells

Summary

Introduction

Cutaneous squamous cell carcinoma ( called cutaneous squamouse cell cancers, CSCC) counts about twenty percent of total skin cancers which is more malignant than basal cell cancers because CSCCs tend to grow and spread much faster than the later. Ultraviolet (UV) exposure is a major cause and directly contributes to the occurrence of CSCC. The current understanding of the molecular mechanism of CSCC is mainly related with transcription factors (TFs), e.g. p53, nuclear factor-kappa B (NF-kB) and activator protein-1 (AP-1) [1]. Mutation or aberrant expression of these TFs contributes directly or indirectly to some or all the cancer hallmarks, including insensitivity to antigrowth or apoptotic signals, self-sufficient growth signals, sustained angiogenesis, limitless replicative potential and invasive or metastatic capability which in turn play important roles in tumorigenesis of CSCC. All the above mechanisms will in turn contribute to the development of skin cancer [4,5]

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