The Klf6-related super enhancer regulates Klf6-SV2 expression mediated proliferation in human hepatoma (HepG2) cells

Chol Kim,Se Hyok O,Sun Il Choe,Kum Chol Ri ,Ju Hyok So

doi:10.1186/s43088-019-0001-4

Abstract

BackgroundThe Klf6 gene, which belongs to Krüppel-like family of C2H2 zinc finger transcription factors, is greatly related to tumorigenesis via a high rate of somatic mutation in the carcinomas of prostate, liver, colon, stomach, lung, neck, pituitary, and nervous system: Furthermore, the pathways regulating the expressions of Klf6 splice variants termed Klf6-SV1, -SV2, and -SV3 remain obscure although their functional outcomes have been clear. In this study, the functional roles of Klf6 variants in the inhibition of cell proliferation induced by the disruption of Klf6-related super enhancer in human hepatoma (HepG2) cells were evaluated.ResultsAs a result, the disruption of Klf6-related super enhancer not only induced the upregulation of Klf6-SV2 but also led to a significant reduction of proliferation in HepG2 cells. In addition, the disruption of Klf6-related super enhancer led to the induction of p21 and Bax genes mediated by the upregulation of Klf6-SV2.ConclusionIn conclusion, it was demonstrated that Klf6-related super enhancer modulates cell proliferation via the regulation of Klf6-SV2 expression in human hepatoma (HepG2) cells. The results provide the functional significance of Klf6-related super enhancer in understanding the transcriptional regulation mechanism of Klf6.

Highlights

The Kruppel-like factor 6 (Klf6) gene, which belongs to Krüppel-like family of C2H2 zinc finger transcription factors, is greatly related to tumorigenesis via a high rate of somatic mutation in the carcinomas of prostate, liver, colon, stomach, lung, neck, pituitary, and nervous system: the pathways regulating the expressions of Klf6 splice variants termed Klf6-SV1, -SV2, and -SV3 remain obscure their functional outcomes have been clear
The results provide the functional significance of Klf6-related super enhancer in understanding the transcriptional regulation mechanism of Klf6
3.1 Deletion of Klf6-related super enhancers (SEs) induces inhibition of cell proliferation in human HepG2 cells A clone of Klf6-related SE deletion (SE-del) clone was obtained using the CRISPR/Cas9 system to evaluate the effect of Klf6-related SE on the expression of Klf6 gene in HepG2 cells

Summary

Introduction

The Klf gene, which belongs to Krüppel-like family of C2H2 zinc finger transcription factors, is greatly related to tumorigenesis via a high rate of somatic mutation in the carcinomas of prostate, liver, colon, stomach, lung, neck, pituitary, and nervous system: the pathways regulating the expressions of Klf splice variants termed Klf6-SV1, -SV2, and -SV3 remain obscure their functional outcomes have been clear. The Klf gene, which belongs to Krüppel-like family (containing C2H2 zinc finger transcription factors), is greatly related to tumorigenesis via a high rate of somatic mutation in the carcinomas of prostate, colon, stomach, liver, lung, neck, pituitary, nervous system, etc. We have already identified a Klf6-related super enhancer in human HepG2 cells using genomic editing techniques and demonstrated that Klf6related SE regulates cellular proliferation as a potent regulator of Klf gene expression [21]. We assumed that regulation of cell proliferation by Klf6-related super enhancer may be associated with Klf variants in deeper study

Methods

Results

Discussion

Conclusion