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

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.

MicroRNA‑34a directly targets high‑mobility group box 1 and inhibits the cancer cell proliferation, migration and invasion in cutaneous squamous cell carcinoma

“…Through regulating the protein expression of their target genes, miRs participate in various cellular biological processes, including cell proliferation, apoptosis, migration, invasion and tumorigenesis (6)(7)(8). In recent years, certain miRs have been implicated in the development and malignant progression of CSCC (9,10). For instance, miR-365 serves a promoting role in CSCC through targeting nuclear factor I/B (9).…”

“…In recent years, certain miRs have been implicated in the development and malignant progression of CSCC (9,10). For instance, miR-365 serves a promoting role in CSCC through targeting nuclear factor I/B (9). In addition, miR-125b directly targets matrix metallopeptidase 13 and inhibits the CSCC cell proliferation, migration, and invasion (10).…”

microRNA-365-targeted nuclear factor I/B transcriptionally represses cyclin-dependent kinase 6 and 4 to inhibit the progression of cutaneous squamous cell carcinoma

“…Further study of this microRNA led to the identification of a downstream target of miR-365, nuclear factor I/B (NFIB) (Zhou et al, 2014). NFIB is a member of the nuclear factor I gene family in vertebrates and has been associated with a diverse set of transcriptional regulatory activities.…”

“…This repression affected downstream cancer-related effectors, including CDK6 (Zhou et al, 2014). Although the role of CDK6 in the initiation and development of tumors has been well-characterized (Kollmann et al, 2013), the underlying mechanism(s) responsible for the regulation of CDK6 by NFIB remain unclear.…”

Role of miR-148a in cutaneous squamous cell carcinoma by repression of MAPK pathway

“…However, cellular function and target genes of miRNAs has not been studied extensively in cutaneous squamous cell carcinoma (CSCC). Previous reports showed that miR-365 [4], miR-199a [5], miRNA-31 [6], miR-193b/365a [7], miRNA-361-5p [8], miR-124/-214 [9] and miRNA-125b [10] play important role in CSCC. miR-148a, a member of the miR-148/152 family, has been found to be downregulated in many types of cancer and its role in cutaneous squamous cell carcinoma remains unknown.…”