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蛋白质精氨酸甲基转移酶5促进肝癌细胞的恶性表型,并与根治性肝切除术后患者的不良预后相关。

The protein arginine methyltransferase 5 promotes malignant phenotype of hepatocellular carcinoma cells and is associated with adverse patient outcomes after curative hepatectomy.

作者信息

Shimizu Dai, Kanda Mitsuro, Sugimoto Hiroyuki, Shibata Masahiro, Tanaka Haruyoshi, Takami Hideki, Iwata Naoki, Hayashi Masamichi, Tanaka Chie, Kobayashi Daisuke, Yamada Suguru, Nakayama Goro, Koike Masahiko, Fujiwara Michitaka, Fujii Tsutomu, Kodera Yasuhiro

机构信息

Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.

出版信息

Int J Oncol. 2017 Feb;50(2):381-386. doi: 10.3892/ijo.2017.3833. Epub 2017 Jan 2.

Abstract

The prognosis of advanced hepatocellular carcinoma (HCC) is dismal. Novel molecular targets for diagnosis and therapy is urgently required. This study evaluated expression and functions of the protein arginine methyltransferase 5 (PRMT5) in HCC. Using HCC cell lines, the expression levels of PRMT5 mRNA were determined using the quantitative real-time reverse-transcription polymerase chain reaction, and the effect of a small interfering PRMT5-siRNA on cell phenotype was evaluated. Further, PRMT5 expression was determined in 144 pairs of resected liver tissues to evaluate its clinical significance. Regardless of their differentiated phenotypes, nine HCC cell lines expressed different levels of PRMT5 mRNA. Inhibition of PRMT5 expression significantly decreased the proliferation, invasion, and migration of HCC cell lines. Although the level of PRMT5 mRNA was not influenced by patient's background liver status, it was significantly higher in HCC tissues than in the corresponding noncancerous tissues. High levels of PRMT5 mRNA in HCC tissues were significantly associated with advanced disease stage and adverse prognosis. In conclusion, our results indicate that PRMT5 may act as a putative oncogene in HCC and that the levels of PRMT5 mRNA represent a promising prognostic marker and a potential target of molecular therapy for HCC.

摘要

晚期肝细胞癌(HCC)的预后很差。迫切需要用于诊断和治疗的新型分子靶点。本研究评估了蛋白精氨酸甲基转移酶5(PRMT5)在HCC中的表达及功能。利用HCC细胞系,采用定量实时逆转录聚合酶链反应测定PRMT5 mRNA的表达水平,并评估小干扰PRMT5-siRNA对细胞表型的影响。此外,在144对切除的肝组织中测定PRMT5表达,以评估其临床意义。无论其分化表型如何,9种HCC细胞系表达不同水平的PRMT5 mRNA。抑制PRMT5表达显著降低了HCC细胞系的增殖、侵袭和迁移能力。虽然PRMT5 mRNA水平不受患者背景肝脏状态的影响,但在HCC组织中显著高于相应的癌旁组织。HCC组织中高水平的PRMT5 mRNA与疾病晚期和不良预后显著相关。总之,我们的结果表明PRMT5可能作为HCC中的一个假定癌基因,且PRMT5 mRNA水平代表了一个有前景的预后标志物以及HCC分子治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d614/5238779/bb89503178cd/IJO-50-02-0381-g00.jpg

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