The 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. As 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. In 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.

中文翻译：

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Klf6 相关的超级增强子调节 Klf6-SV2 表达介导的人肝癌 (HepG2) 细胞增殖

Klf6 基因属于 Krüppel 样 C2H2 锌指转录因子家族，通过在前列腺癌、肝癌、结肠癌、胃癌、肺癌、颈癌、垂体癌和神经癌中的高体细胞突变率与肿瘤发生密切相关。系统：此外，调节称为 Klf6-SV1、-SV2 和 -SV3 的 Klf6 剪接变体表达的途径仍然不清楚，尽管它们的功能结果已经很清楚。在这项研究中，评估了 Klf6 变体在抑制人肝癌 (HepG2) 细胞中 Klf6 相关超增强子破坏诱导的细胞增殖中的功能作用。因此，Klf6 相关超级增强子的破坏不仅诱导了 Klf6-SV2 的上调，而且还导致 HepG2 细胞增殖的显着减少。此外，Klf6 相关超级增强子的破坏导致了由 Klf6-SV2 上调介导的 p21 和 Bax 基因的诱导。总之，已证明 Klf6 相关的超级增强子通过调节人肝癌 (HepG2) 细胞中 Klf6-SV2 的表达来调节细胞增殖。该结果提供了 Klf6 相关超级增强子在理解 Klf6 转录调控机制方面的功能意义。