Non-Coding RNAs as Regulators and Markers for Targeting of Breast Cancer and Cancer Stem Cells

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Abstract

Breast cancer is regarded as a heterogeneous and complicated disease that remains the prime focus in the domain of public health concern. Next-generation sequencing technologies provided a new perspective dimension to non-coding RNAs, which were initially considered to be transcriptional noise or a product generated from erroneous transcription. Even though understanding of biological and molecular functions of noncoding RNA remains enigmatic, researchers have established the pivotal role of these RNAs in governing a plethora of biological phenomena that includes cancer-associated cellular processes such as proliferation, invasion, migration, apoptosis, and stemness. In addition to this, the transmission of microRNAs and long non-coding RNAs was identified as a source of communication to breast cancer cells either locally or systemically. The present review provides in-depth information with an aim at discovering the fundamental potential of non-coding RNAs, by providing knowledge of biogenesis and functional roles of micro RNA and long non-coding RNAs in breast cancer and breast cancer stem cells, as either oncogenic drivers or tumor suppressors. Furthermore, non-coding RNAs and their potential role as diagnostic and therapeutic moieties have also been summarized.

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Hypoxia in cancer: significance and impact on clinical outcome.

Peter Vaupel, Arnulf Mayer (2007)

Hypoxia, a characteristic feature of locally advanced solid tumors, has emerged as a pivotal factor of the tumor (patho-)physiome since it can promote tumor progression and resistance to therapy. Hypoxia represents a "Janus face" in tumor biology because (a) it is associated with restrained proliferation, differentiation, necrosis or apoptosis, and (b) it can also lead to the development of an aggressive phenotype. Independent of standard prognostic factors, such as tumor stage and nodal status, hypoxia has been suggested as an adverse prognostic factor for patient outcome. Studies of tumor hypoxia involving the direct assessment of the oxygenation status have suggested worse disease-free survival for patients with hypoxic cervical cancers or soft tissue sarcomas. In head & neck cancers the studies suggest that hypoxia is prognostic for survival and local control. Technical limitations of the direct O(2) sensing technique have prompted the use of surrogate markers for tumor hypoxia, such as hypoxia-related endogenous proteins (e.g., HIF-1alpha, GLUT-1, CA IX) or exogenous bioreductive drugs. In many - albeit not in all - studies endogenous markers showed prognostic significance for patient outcome. The prognostic relevance of exogenous markers, however, appears to be limited. Noninvasive assessment of hypoxia using imaging techniques can be achieved with PET or SPECT detection of radiolabeled tracers or with MRI techniques (e.g., BOLD). Clinical experience with these methods regarding patient prognosis is so far only limited. In the clinical studies performed up until now, the lack of standardized treatment protocols, inconsistencies of the endpoints characterizing the oxygenation status and methodological differences (e.g., different immunohistochemical staining procedures) may compromise the power of the prognostic parameter used.

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Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells.

Sabine Loewer, Moran Cabili, Mitchell Guttman … (2010)

The conversion of lineage-committed cells to induced pluripotent stem cells (iPSCs) by reprogramming is accompanied by a global remodeling of the epigenome, resulting in altered patterns of gene expression. Here we characterize the transcriptional reorganization of large intergenic non-coding RNAs (lincRNAs) that occurs upon derivation of human iPSCs and identify numerous lincRNAs whose expression is linked to pluripotency. Among these, we defined ten lincRNAs whose expression was elevated in iPSCs compared with embryonic stem cells, suggesting that their activation may promote the emergence of iPSCs. Supporting this, our results indicate that these lincRNAs are direct targets of key pluripotency transcription factors. Using loss-of-function and gain-of-function approaches, we found that one such lincRNA (lincRNA-RoR) modulates reprogramming, thus providing a first demonstration for critical functions of lincRNAs in the derivation of pluripotent stem cells.

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Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal.

Yue Wang, Zhenyu Xu, Junfeng Jiang … (2013)

The embryonic stem cell (ESC) transcriptional and epigenetic networks are controlled by a multilayer regulatory circuitry, including core transcription factors (TFs), posttranscriptional modifier microRNAs (miRNAs), and some other regulators. However, the role of large intergenic noncoding RNAs (lincRNAs) in this regulatory circuitry and their underlying mechanism remains undefined. Here, we demonstrate that a lincRNA, linc-RoR, may function as a key competing endogenous RNA to link the network of miRNAs and core TFs, e.g., Oct4, Sox2, and Nanog. We show that linc-RoR shares miRNA-response elements with these core TFs and that linc-RoR prevents these core TFs from miRNA-mediated suppression in self-renewing human ESC. We suggest that linc-RoR forms a feedback loop with core TFs and miRNAs to regulate ESC maintenance and differentiation. These results may provide insights into the functional interactions of the components of genetic networks during development and may lead to new therapies for many diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

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Journal

Journal ID (nlm-ta): Cancers (Basel)

Journal ID (iso-abbrev): Cancers (Basel)

Journal ID (publisher-id): cancers

Title: Cancers

Publisher: MDPI

ISSN (Electronic): 2072-6694

Publication date (Electronic): 04 February 2020

Publication date Collection: February 2020

Volume: 12

Issue: 2

Electronic Location Identifier: 351

Affiliations

[1 ]Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar; hamnafathima2001@ 123456gmail.com (H.F.); emoibrahim04@ 123456gmail.com (E.I.A.); SKuttikrishnan@ 123456hamad.qa (S.K.); LTherachiyil@ 123456hamad.qa (L.T.); MKulinski@ 123456hamad.qa (M.K.); MSteinhoff@ 123456hamad.qa (M.S.); skhan34@ 123456hamad.qa (S.U.)

[2 ]National Center for Cancer Care and Research, Hamad Medical Corporation, Doha 3050, Qatar; ARaza@ 123456hamad.qa (A.R.); SDermime@ 123456hamad.qa (S.D.)

[3 ]Sidra Medicine, Doha 26999, Qatar; tkaredathabdulazis@ 123456sidra.org

[4 ]Department of Stem Cell Biology and Regenerative Medicine, Era University, Lucknow 226003, India; drshadab@ 123456erauniversity.in

[5 ]Qatar College of Pharmacy, Qatar University, Doha 3050, Qatar

[6 ]General Surgery Department, Hamad General Hospital, Hamad Medical Corporation, Doha 3050, Qatar; KJunejo@ 123456hamad.qa

[7 ]Department of Dermatology Venereology, Hamad Medical Corporation, Doha 3050, Qatar

[8 ]Department of Dermatology, Weill Cornell Medicine, Qatar Foundation, Education City, Doha 24144, Qatar

[9 ]Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA

Author notes

[* ]Correspondence: KPrabhu@ 123456hamad.qa ; Tel.: +974-4439-0966

[†]

These authors contributed equally to this paper.

Author information

Thasni Karedath https://orcid.org/0000-0001-5482-5954

Syed Shadab Raza https://orcid.org/0000-0002-6147-9399

Said Dermime https://orcid.org/0000-0002-5526-7496

Shahab Uddin https://orcid.org/0000-0003-1886-6710

Article

Publisher ID: cancers-12-00351

DOI: 10.3390/cancers12020351

PMC ID: 7072613

PubMed ID: 32033146

SO-VID: b0dc6944-5754-49a0-bb3b-92795cdf50f6

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Non-Coding RNAs as Regulators and Markers for Targeting of Breast Cancer and Cancer Stem Cells

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Most cited references 156

Hypoxia in cancer: significance and impact on clinical outcome.

Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells.

Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal.

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