Therapeutic targeting of noncoding RNAs in hepatocellular carcinoma: Recent progress and future prospects

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Abstract

Due to the high mortality rate and unsatisfactory treatment options available, hepatocellular carcinoma (HCC) remains one of the most common malignancies and a leading cause of cancer-associated mortality. Novel therapeutic targets for HCC are urgently required. Advanced RNA sequencing technology enables the identification of considerable amounts of noncoding RNAs (ncRNAs), including small noncoding RNAs and long noncoding RNAs, which exhibit no protein-coding activities. In this respect, ncRNAs and their regulatory processes are important factors in liver tumorigenesis. The present review focuses on the characteristics and biological roles of ncRNAs in HCC. Potential therapeutic applications of ncRNAs in HCC are also evaluated.

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Most cited references 81

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A germline-specific class of small RNAs binds mammalian Piwi proteins.

Angélique Girard, Ravi Sachidanandam, Gregory Hannon … (2006)

Small RNAs associate with Argonaute proteins and serve as sequence-specific guides to regulate messenger RNA stability, protein synthesis, chromatin organization and genome structure. In animals, Argonaute proteins segregate into two subfamilies. The Argonaute subfamily acts in RNA interference and in microRNA-mediated gene regulation using 21-22-nucleotide RNAs as guides. The Piwi subfamily is involved in germline-specific events such as germline stem cell maintenance and meiosis. However, neither the biochemical function of Piwi proteins nor the nature of their small RNA guides is known. Here we show that MIWI, a murine Piwi protein, binds a previously uncharacterized class of approximately 29-30-nucleotide RNAs that are highly abundant in testes. We have therefore named these Piwi-interacting RNAs (piRNAs). piRNAs show distinctive localization patterns in the genome, being predominantly grouped into 20-90-kilobase clusters, wherein long stretches of small RNAs are derived from only one strand. Similar piRNAs are also found in human and rat, with major clusters occurring in syntenic locations. Although their function must still be resolved, the abundance of piRNAs in germline cells and the male sterility of Miwi mutants suggest a role in gametogenesis.

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Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells.

Alexander Marson, Stuart S. Levine, Megan Cole … (2008)

MicroRNAs (miRNAs) are crucial for normal embryonic stem (ES) cell self-renewal and cellular differentiation, but how miRNA gene expression is controlled by the key transcriptional regulators of ES cells has not been established. We describe here the transcriptional regulatory circuitry of ES cells that incorporates protein-coding and miRNA genes based on high-resolution ChIP-seq data, systematic identification of miRNA promoters, and quantitative sequencing of short transcripts in multiple cell types. We find that the key ES cell transcription factors are associated with promoters for miRNAs that are preferentially expressed in ES cells and with promoters for a set of silent miRNA genes. This silent set of miRNA genes is co-occupied by Polycomb group proteins in ES cells and shows tissue-specific expression in differentiated cells. These data reveal how key ES cell transcription factors promote the ES cell miRNA expression program and integrate miRNAs into the regulatory circuitry controlling ES cell identity.

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Molecular signals of epigenetic states.

Roberto Bonasio, Shengjiang Tu, Danny Reinberg (2010)

Epigenetic signals are responsible for the establishment, maintenance, and reversal of metastable transcriptional states that are fundamental for the cell's ability to "remember" past events, such as changes in the external environment or developmental cues. Complex epigenetic states are orchestrated by several converging and reinforcing signals, including transcription factors, noncoding RNAs, DNA methylation, and histone modifications. Although all of these pathways modulate transcription from chromatin in vivo, the mechanisms by which epigenetic information is transmitted through cell division remain unclear. Because epigenetic states are metastable and change in response to the appropriate signals, a deeper understanding of their molecular framework will allow us to tackle the dysregulation of epigenetics in disease.

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Author and article information

Journal

Journal ID (nlm-ta): Oncol Lett

Journal ID (iso-abbrev): Oncol Lett

Journal ID (publisher-id): OL

Title: Oncology Letters

Publisher: D.A. Spandidos

ISSN (Print): 1792-1074

ISSN (Electronic): 1792-1082

Publication date (Print): March 2018

Publication date (Electronic): 09 January 2018

Publication date PMC-release: 09 January 2018

Volume: 15

Issue: 3

Pages: 3395-3402

Affiliations

[1 ]Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China

[2 ]School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China

Author notes

Correspondence to: Dr Zhangang Xiao, Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, 319 Zhongshan Road, 3rd Section, Luzhou, Sichuan 646000, P.R. China, E-mail: xzg555898@ 123456hotmail.com

Professor Chihin Cho, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, East New Territories, Hong Kong SAR, P.R. China, E-mail: chcho@ 123456cuhk.edu.hk

Article

Publisher ID: OL-0-0-7758

DOI: 10.3892/ol.2018.7758

PMC ID: 5796293

PubMed ID: 29467864

SO-VID: c9f8a401-086f-4849-a405-5635f1840bb8

License:

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Therapeutic targeting of noncoding RNAs in hepatocellular carcinoma: Recent progress and future prospects

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Abstract

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Karger: Oncology

Most cited references 81

A germline-specific class of small RNAs binds mammalian Piwi proteins.

Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells.

Molecular signals of epigenetic states.

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