Background:
Recent studies have attempted to elucidate the function of super enhancers
by means of microRNAs. Although the functional outcomes of miR-1301 have become clearer, the
pathways that regulate the expressions of miR-1301 remain unclear.
Objective:
The objective of this paper was to consider the pathway regulating expression of miR-
1301 and miR-1301 signaling pathways with the inhibition of cell proliferation.
Methods:
In this study, we prepared the cell clones that the KLF6 super enhancer was deleted by
means of the CRISPR/Cas9 system-mediated genetic engineering. Changes in miR-1301 expression
after the deletion of the KLF6 super enhancer were evaluated by RT-PCR analysis, and the signal
pathway of miR-1301 with inhibition of the cell proliferation was examined using RNA interference
technology.
Results:
The results showed that miR-1301 expression was significantly increased after the deletion
of the KLF6 super enhancer. Over-expression of miR-1301 induced by deletion of the KLF6 super
enhancer also regulated the expression of p21 and p53 in human hepatoma cells. functional modeling
of findings using siRNA specific to miR-1301 showed that expression level changes had direct biological
effects on cellular proliferation in Human hepatoma cells. Furthermore, cellular proliferation
assay was shown to be directly associated with miR-1301 levels.
Conclusion:
As a result, it was demonstrated that the over-expression of miR-1301 induced by the
disruption of the KLF6 super enhancer leads to a significant inhibition of proliferation in HepG2
cells. Moreover, it was demonstrated that the KLF6 super enhancer regulates the cell-proliferative effects
which are mediated, at least in part, by the induction of p21and p53 in a p53-dependent manner.
Our results provide the functional significance of miR-1301 in understanding the transcriptional regulation
mechanism of the KLF6 super enhancer.
Palmitic acid induced lipotoxicity is associated with altered lipid metabolism, enhanced CYP450 2E1 and intracellular calcium mediated ER stress in human hepatoma cells
