Journal Article

LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3

Zhu, Yuekun, Li, Huanyu, Sun, Ziquan, Han, Zhiyang, Zhu, Anlong, Liu, Tianyou

2018

Overview

Background Accumulating evidences show that long noncoding RNAs (lncRNA) play essential roles in the development and progression of various malignancies. However, their functions remains poorly understood and many lncRNAs have not been defined in colorectal cancer (CRC). In this study, we investigated the role of DLEU1 in CRC. Methods Quantitative real-time PCR was used to detect the expression of DLEU1 and survival analysis was adopted to explore the association between DLEU1 expression and the prognosis of CRC patients. CRC cells were stably transfected with lentivirus approach and cell proliferation, migration, invasion and cell apoptosis, as well as tumorigenesis in nude mice were performed to assess the effects of DLEU1 in BCa. Biotin-coupled probe pull down assay, RNA immunoprecipitation and Fluorescence in situ hybridization assays were conducted to confirm the relationship between DLEU1 and SMARCA1. Results Here we revealed that DLEU1 was crucial for activation of KPNA3 by recruiting SMARCA1, an essential subunit of the NURF chromatin remodeling complex, in CRC. DLEU1 was indispensible for the deposition of SMARCA1 at the promoter of KPNA3 gene. Increased expression of DLEU1 and KPNA3 was observed in human CRC tissues. And higher expression of DLEU1 or KPNA3 in patients indicates lower survival rate and poorer prognosis. DLEU1 knockdown remarkably inhibited CRC cell proliferation, migration and invasion in vitro and in vivo while overexpressing KPNA3 in the meantime reversed it. Conclusions Our results identify DLEU1 as a key regulator by a novel DLEU1/SMARCA1/KPNA3 axis in CRC development and progression, which may provide a potential biomarker and therapeutic target for the management of CRC.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: alpha Karyopherins - genetics / Analysis / Animals / Apoptosis / Biological markers / Biomedical and Life Sciences / Biomedicine / Biotin / Breast cancer / Caco-2 Cells / Cancer Research / Cancer therapies / Care and treatment / Cell growth / Cell Line, Tumor / Cell migration / Cell Movement / Cell Proliferation / Chromatin remodeling / Cloning / Colorectal cancer / Colorectal carcinoma / Colorectal Neoplasms - genetics / Colorectal Neoplasms - metabolism / Colorectal Neoplasms - pathology / Development and progression / DLEU1 / DNA-Binding Proteins - genetics / DNA-Binding Proteins - metabolism / Epigenesis, Genetic / Fluorescence in situ hybridization / Gastric cancer / Gene expression / Gene Expression Regulation, Neoplastic / HCT116 Cells / Hospitals / HT29 Cells / Humans / Immunoprecipitation / KPNA3 / Liver cancer / Male / Medical prognosis / Mice / Neoplasm Transplantation / Oncology / Prognosis / Progression / Promoter Regions, Genetic / Ribonucleic acid / RNA / RNA probes / SMARCA1 / Survival analysis / Therapeutic applications / Transcription Factors - genetics / Transcription Factors - metabolism / Transcriptional Activation / Tumor Suppressor Proteins - genetics / Tumorigenesis / Up-Regulation