MiR-27a as a predictor for the activation of hepatic stellate cells and hepatitis B virus-induced liver cirrhosis

Makarova

et al. 2019

Cells

The incidence and mortality of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HBV-HCC) is an intractable public health problem in developing countries that is compounded by limited early detection and therapeutic options. Despite the early promise of utilizing the regulatory role of miRNA in liver cancer, this field remains largely in the work-in-progress phase. This exploratory review paper adopts a broad focus in order to collate evidence of the regulatory role of miRNA in each stage of the HBV-HCC continuum. This includes the regulatory role of miRNA in early HBV infection, chronic inflammation, fibrosis/cirrhosis, and the onset of HCC. The paper specifically investigates HBV dysregulated miRNA that influence the expression of the host/HBV genome in HBV-HCC pathogenesis and fully acknowledges that this does not cover the full spectrum of dysregulated miRNA. The sheer number of dysregulated miRNA in each phase support a hypothesis that future therapeutic interventions will need to consider incorporating multiple miRNA panels.An estimated 841,080 new liver cancers (LCs) were diagnosed worldwide in 2018, with hepatocellular carcinoma (HCC), the most common histological subtype, accounting for 75% to 90% of LCs [1]. A 12.4% increase of LC was recorded between 2008 (696,000) to 2012 (782,000) [2] and [3] 7.6% between 2012 and 2018 (841,080) [1]. HCC is listed globally as a leading cancer in men and women [4], with a recent report indicating that 83% of new cases diagnosed occurred in less well

Section: Mirna Regulating Hbv-induced Fibrosis/cirrhosismentioning

confidence: 99%

The Regulatory Role of MicroRNA in Hepatitis-B Virus-Associated Hepatocellular Carcinoma (HBV-HCC) Pathogenesis

Makarova

et al. 2019

Cells

Evidence-Based Complementary and Alternative Medicine

“…e human hepatocyte L02 cell line was purchased from the Cell Bank of Chinese Academy of Sciences (Shanghai, China). Cell culture conditions and cell treatments were as previously described [26]. Exponentially growing LX2 cells were treated with 10 ng/ml TGF-β1 (R&D Systems, Shanghai, China) for 24 h or 48 h, and then cells were collected for miRNA isolation and RT-qPCR analysis.…”

Section: Cell Culture and Treatmentsmentioning

confidence: 99%

“…Analysis. RNA isolation and quantitative real-time RT-PCR (RT-qPCR) was carried out as previously described [26]. Primers for miR-663a and U6 (RT-qPCR Primer Set) were purchased from Guangzhou RuiBio Corp. (Guangzhou, China).…”

Section: Rna Isolation and Quantitative Real-time Rt-pcrmentioning

confidence: 99%

Glycyrrhetinic Acid‐Induced MiR‐663a Alleviates Hepatic Stellate Cell Activation by Attenuating the TGF‐β/Smad Signaling Pathway

Guo

Yang

Dong

et al. 2020

Self Cite

Glycyrrhetinic acid (GA), a hydrolysate of glycyrrhizic acid from licorice root extract, has been used to treat liver fibrotic diseases. However, the molecular mechanism involved in the antifibrotic effects of GA remains unclear. The involvement of miR-663a and its roles in TGF-β-1-induced hepatic stellate cell (HSC) activation remains unclear. In this study, we investigated the roles of miR-663a in the activation of HSCs and the antifibrosis mechanism of GA. MiR-663a expression was downregulated in TGF-β-treated HSCs. The overexpression of miR-663a inhibited HSC proliferation. TGF-β-1was confirmed as a direct target gene of miR-663a. MiR-663a alleviated HSC activation, concomitant with decreased expression of α-smooth muscle actin (α-SMA), human α2 (I) collagen (COL1A2), TGF-β1, TGF-βRI, Smad4, p-Smad2, and p-Smad3. GA upregulated miR-663a expression and inhibited the TGF-β/Smad pathway in HSCs. Further studies showed that miR-663a inhibitor treatment reversed GA-mediated downregulation of TGF-β1, TGF-βRI, Smad4, p-Smad2, p-Smad3, α-SMA, and CoL1A2 in TGF-β1-treated HSCs. These results show that miR-663a suppresses HSC proliferation and activation and the TGF-β/Smad signaling pathway, highlighting that miR-663a can be utilized as a therapeutic target for hepatic fibrosis. GA inhibits, at least in part, HSC proliferation and activation via targeting the miR-663a/TGF-β/Smad signaling pathway.

“…Several studies have shown that miR-27a is overexpressed in liver stellate cells, influencing fat accumulation and cell proliferation, leading to hepatic fibrosis (83). It was also proven that miR-27a can induce liver fibrosis and be used as a diagnostic biomarker in advanced liver fibrosis and cirrhosis with hepatitis viruses B and C (84).…”

Section: Mir-27a In Promoting Tumorigenesismentioning

confidence: 99%

MicroRNA-27a (miR-27a) in Solid Tumors: A Review Based on Mechanisms and Clinical Observations

Zhang

Cao

et al. 2019

Front. Oncol.

MicroRNAs (miRNAs) are a family of highly conserved, non-coding single-stranded RNAs transcribed as ~70 nucleotide precursors to an 18–22 nucleotide product (1). miRNAs can silence their homologous target genes at the post-transcriptional level, and these genes have been revealed to play an important role in tumorigenesis, invasion and metastasis (2). MicroRNA-27a (miR-27a), transcripted by miR-27a gene, has proved to implicate with many kinds of solid tumors, showing potential as a useful biomarker or drug target for clinical application. However, even though miR-27a has been reported in many cancers, the mechanism and signal pathways of miR-27 in oncogenesis, invasion, and metastasis are still obscure. Moreover, recent studies show that miR-27a pays an important role in epithelial-mesenchymal-transition, regulating tumor immune response, and chemoresistance. In this review, we summarize the current literature, demonstrate the established link between miR-27a and tumorigenesis, and focus on recently identified mechanisms. The review also aims to demonstrate the potential of miR-27a as a diagnostic and/or prognostic biomarker in solid tumors and to discuss the possibilities of targeted therapy and drug design.