RN7SL1 overexpression promotes cell proliferation in cutaneous T-cell lymphoma via miR-34a-5p/MYCN axis

Abstract

Background

Cutaneous T-cell lymphoma (CTCL) is a type of lymphoma that presents in skin tissue without evidence of extracutaneous disease. Emerging evidence indicates that long noncoding RNA-RN7SL1 serves as crucial effectors in modulating progression of different malignancies, including breast cancer, liver cancer, and other neoplasms.

Objective

To figure out the role of RN7SL1 in the pathogenesis of CTCL.

Methods

We detected RN7SL1 expression of CTCL patients by quantitative real-time polymerase chain reaction and fluorescent in situ hybridization. CTCL cell lines were transfected with lentiviral-based RN7SL1 gene knockdown vectors. Whole transcriptome sequencing was conducted to investigate differentially expressed miRNA and mRNA in CTCL, and we used qRT-PCR, RNA immunoprecipitation, dual-luciferase assay, RNA pull down and Western Blotting to further detect the relation of miRNA and mRNA. Also, we have verified above results in mice and clinical samples.

Results

LncRNA-RN7SL1 was overexpressed in CTCL compared with benign inflammatory dermatosis and was related to the TNMB stage of mycosis fungoides and Sézary syndrome (higher expression in IIB-IVB stage than IA-IIA stage). Additionally, the proliferation of CTCL cell lines HH and Hut78 was weakened, but apoptosis was facilitated by RN7SL1 downregulation, resulting in a reduced tumorigenic capacity in vivo. Subsequently, Whole transcriptome sequencing and target validation indicated that the RN7SL1/miR-34a-5p/MYCN axis may promoted malignant behavior in CTCL.

Conclusion

Our study suggested that RN7SL1 promoted malignant behavior by targeting miR-34a-5p/MYCN signaling. This finding might facilitate the discovery of novel biomarkers for CTCL diagnosis and treatment.