Abstract
BackgroundJumonji AT-rich interactive domain 1B(JARID1B) has been shown to be upregulated in many human cancers and plays a critical role in the development of cancers cells. Nevertheless, its functional role in colorectal cancer (CRC) progression is not fully understood.MethodsHerein, JARID1B expression levels were detected in clinical CRC samples by western blotting and qRT-PCR. DLD-1 cells with JARID1B knockdown or overexpression by stably transfected plasmids were used in vitro and in vivo study. Colony formation, 5-ethynyl-20-deoxyuridine (EdU) and Real Time Cellular Analysis (RTCA) assays were used to detect cell proliferation and growth. Transcriptome and CHIP assays were used to examine the molecular biology changes and molecular interaction in these cells. Nude mice was utilized to study the correlation of JARID1B and tumor growth in vivo.ResultsHere, we first observed that JARID1B was significantly upregulated in CRC tissue compared to adjacent normal tissues. In CRC patients, JARID1B high expression was positively relation with poor overall survival. Multivariate analyses revealed that high JARID1B expression was an independent predictive marker for the poor prognosis of CRC. In addition, we found that JARID1B promoted CRC cells proliferation by Wnt/β-catenin signaling pathway. Further studies demonstrated CDX2 as a downstream target of JARID1B, and our data demonstrated that CDX2 is crucial for JARID1B -mediated Wnt/β-catenin signaling pathway. Mechanistically, we demonstrated that JARID1B regulated CDX2 expression through demethylation of H3K4me3.ConclusionsCDX2 inhibited by JARID1B-derived H3K4me3 methylation promoted cells proliferation of CRC via Wnt/β-catenin signaling pathway. Therefore, our studies provided a novel insight into the role of JARID1B in CRC cells proliferation and potential new molecular target for treating CRC.7iDCCN6fi_Z-Myd1SxMdsEVideo abstractGraphical abstract
Highlights
Jumonji AT-rich interactive domain 1B(JARID1B) has been shown to be upregulated in many human cancers and plays a critical role in the development of cancers cells
We found that JARID1B was elevated in colorectal cancer (CRC) tissues compared with normal colonic tissues using quantitative reverse transcription-PCR, western blot and immunohistochemistry
JARID1B was markedly upregulated in CRC tissues and was closely related to CRC progression To investigate the role of JARID1B in the development of colorectal cancer, we investigated JARID1B expression levels in colorectal cancer, and 54 paired fresh CRC tissue samples and matched adjacent non-tumour tissues were used. quantitative reverse transcriptase PCR (qRT-PCR) revealed that the mRNA expression level of JARID1B was notably elevated in CRC tissue samples compared with the corresponding adjacent tissues (Fig. 1a, b)
Summary
Jumonji AT-rich interactive domain 1B(JARID1B) has been shown to be upregulated in many human cancers and plays a critical role in the development of cancers cells. Colorectal cancer (CRC) is the most common cancer with high morbidity worldwide and is the third leading cause of cancer-related death in men and the second leading cause in women [1, 2]. Diagnosis and treatment techniques have improved and new cancer therapeutics, including molecular targeted therapies and immunotherapies, have occurred, cancer prognosis is still unsatisfactory because of the dysregulation of cell death and proliferation mechanisms in cancer [3, 4]. Epigenetic regulation of gene expression has been shown to provide new insights into the pathogenesis of CRC [6]. We showed that a new target related to histone methylation modification can regulate CRC cell proliferation
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