HBV感染通過miR-181a / 382/362 / 19a的上調加劇了肝癌PTEN缺陷

StephenW

Am J Transl Res

. 2020 Jul 15;12(7):3780-3791.
eCollection 2020.
HBV infection exacerbates PTEN defects in hepatocellular carcinoma through upregulation of miR-181a/382/362/19a
Simin Ma  1   2 , Kai Qin  1   3 , Hui Ouyang  1 , Huifen Zhu  1 , Ping Lei  1 , Guanxin Shen  1
Affiliations

    PMID: 32774734 PMCID: PMC7407694

Abstract

A high hepatitis B virus (HBV) load and chronic hepatitis B infection are well-recognized risk factors for the development of hepatocellular carcinoma (HCC), highlighting the need for research into the mechanisms underlying the role of HBV infection in HCC. Because phosphatase and tensin homolog (PTEN) has been implicated in HCC development, we explored whether PTEN has a role in HBV-related hepatocarcinogenesis. We found that PTEN expression was correlated with advanced clinicopathological features and that HBV infection exacerbates PTEN defects in HCC. Using an integrated approach, we then investigated if miRNAs linked HBV infection to PTEN downregulation in HCC and found that PTEN was a target of miR-181a/382/362/19a. We also show that miR-181a/382/362/19a-mediated inhibition of PTEN led to an enhanced malignant phenotype and stimulation of AKT signaling in HCC cells. Collectively, our results indicate that HBV infection exacerbates PTEN defects in hepatocellular carcinoma through upregulation of miR-181a/362/382/19a. Our work implicates miR-181a/362/382/19a and PTEN as potential biomarkers and targets for novel prognostic, diagnostic, and therapeutic strategies targeting HBV-related HCC.

Keywords: HBV; hepatocellular carcinoma; microRNA; phosphatase and tensin homolog deleted on chromosome 10.

AJTR Copyright © 2020.

StephenW

美國翻譯雜誌

。 2020 Jul 15; 12（7）：3780-3791。
eCollection 2020。
HBV感染通過miR-181a / 382/362 / 19a的上調加劇了肝癌PTEN缺陷
馬思敏1 2，開勤1 3，歐陽陽1，朱慧芬1，平雷1，官信深1
隸屬關係

    PMID：32774734 PMCID：PMC7407694

抽象

乙肝病毒（HBV）高負荷和慢性乙肝感染是肝細胞癌（HCC）發生的公認危險因素，這突出表明有必要研究HBV感染在HCC中的潛在作用機制。由於磷酸酶和張力蛋白同源物（PTEN）已參與HCC的發展，因此我們探討了PTEN是否在HBV相關的肝癌發生中起作用。我們發現PTEN表達與晚期臨床病理特徵相關，並且HBV感染加劇了肝癌中PTEN的缺陷。然後，使用整合的方法，我們調查了miRNA是否將HBV感染與HCC中PTEN的下調聯繫起來，並發現PTEN是miR-181a / 382/362 / 19a的靶標。我們還顯示，miR-181a / 382/362 / 19a介導的PTEN抑制導致HCC細胞中惡性表型的增強和AKT信號的刺激。總體而言，我們的結果表明，HBV感染通過上調miR-181a / 362/382 / 19a加劇了肝癌中的PTEN缺陷。我們的工作暗示miR-181a / 362/382 / 19a和PTEN是潛在的生物標誌物，是針對HBV相關HCC的新的預後，診斷和治療策略的靶標。

關鍵字：HBV；肝細胞癌；微小RNA 10號染色體上缺失的磷酸酶和張力蛋白同源物

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