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抑制热休克转录因子抑制肝癌细胞增殖和细胞周期进展通过下调 CCND1 表达。

Knockdown of Hotair suppresses proliferation and cell cycle progression in hepatocellular carcinoma cell by downregulating CCND1 expression.

机构信息

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.

Laboratory of Biomechanics and Physiology, Guangdong Provincial Institute of Sports Science, Guangzhou, Guangdong 510663, P.R. China.

出版信息

Mol Med Rep. 2017 Oct;16(4):4980-4986. doi: 10.3892/mmr.2017.7162. Epub 2017 Aug 3.

Abstract

The long noncoding RNA, homeobox transcript antisense RNA (Hotair), has been demonstrated to have an important role in regulating various biological processes in various cancers, including hepatocellular carcinoma (HCC). However, the importance of Hotair in HCC proliferation and cell cycle progression remains to be elucidated. In the present study, knockdown of HOTAIR expression by RNA interference inhibited cell proliferation and induced G0/G1 cell cycle arrest in Huh7 hepatocellular carcinoma cells. In addition, the expression levels of CCND1 mRNA and its cyclin D1 protein product were reduced in Huh7 cells following knockdown of HOTAIR. Knockdown of HOTAIR reduced the expression of phosphorylated signal transducer and activator of transcription 3 (STAT3) and HOTAIR knockdown combined with STAT3 inhibition led to an additional decrease in cyclin D1 expression. The present study suggested that Hotair may have a critical role in the proliferation of HCC by regulating cell cycle, STAT3 activity and cyclin D1 expression. Therefore, Hotair may be a novel potential therapeutic target for HCC treatment.

摘要

长链非编码 RNA,同源盒转录反义 RNA(Hotair)已被证明在多种癌症中,包括肝细胞癌(HCC)中,在调节各种生物学过程中具有重要作用。然而,Hotair 在 HCC 增殖和细胞周期进展中的重要性仍有待阐明。在本研究中,通过 RNA 干扰敲低 HOTAIR 的表达抑制了 Huh7 肝癌细胞的增殖并诱导了 G0/G1 细胞周期停滞。此外,敲低 HOTAIR 后 Huh7 细胞中 CCND1 mRNA 及其细胞周期蛋白 D1 蛋白产物的表达减少。敲低 HOTAIR 降低了磷酸化信号转导和转录激活因子 3(STAT3)的表达,而 HOTAIR 敲低与 STAT3 抑制相结合导致细胞周期蛋白 D1 表达进一步降低。本研究表明,Hotair 可能通过调节细胞周期、STAT3 活性和细胞周期蛋白 D1 表达在 HCC 增殖中发挥关键作用。因此,Hotair 可能是 HCC 治疗的一个新的潜在治疗靶点。

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