Molecular Landscape of LncRNAs in Prostate Cancer: A focus on pathways and therapeutic targets for intervention

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Abstract

Background

One of the most malignant tumors in men is prostate cancer that is still incurable due to its heterogenous and progressive natures. Genetic and epigenetic changes play significant roles in its development. The RNA molecules with more than 200 nucleotides in length are known as lncRNAs and these epigenetic factors do not encode protein. They regulate gene expression at transcriptional, post-transcriptional and epigenetic levels. LncRNAs play vital biological functions in cells and in pathological events, hence their expression undergoes dysregulation.

Aim of review

The role of epigenetic alterations in prostate cancer development are emphasized here. Therefore, lncRNAs were chosen for this purpose and their expression level and interaction with other signaling networks in prostate cancer progression were examined.

Key scientific concepts of review

The aberrant expression of lncRNAs in prostate cancer has been well-documented and progression rate of tumor cells are regulated via affecting STAT3, NF-κB, Wnt, PI3K/Akt and PTEN, among other molecular pathways. Furthermore, lncRNAs regulate radio-resistance and chemo-resistance features of prostate tumor cells. Overexpression of tumor-promoting lncRNAs such as HOXD-AS1 and CCAT1 can result in drug resistance. Besides, lncRNAs can induce immune evasion of prostate cancer via upregulating PD-1. Pharmacological compounds such as quercetin and curcumin have been applied for targeting lncRNAs. Furthermore, siRNA tool can reduce expression of lncRNAs thereby suppressing prostate cancer progression. Prognosis and diagnosis of prostate tumor at clinical course can be evaluated by lncRNAs. The expression level of exosomal lncRNAs such as lncRNA-p21 can be investigated in serum of prostate cancer patients as a reliable biomarker.

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Most cited references 299

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Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)

This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.

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Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy.

Padmanee Sharma, Siwen Hu-Lieskovan, Jennifer A. Wargo … (2017)

Cancer immunotherapy can induce long lasting responses in patients with metastatic cancers of a wide range of histologies. Broadening the clinical applicability of these treatments requires an improved understanding of the mechanisms limiting cancer immunotherapy. The interactions between the immune system and cancer cells are continuous, dynamic, and evolving from the initial establishment of a cancer cell to the development of metastatic disease, which is dependent on immune evasion. As the molecular mechanisms of resistance to immunotherapy are elucidated, actionable strategies to prevent or treat them may be derived to improve clinical outcomes for patients.

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The multilayered complexity of ceRNA crosstalk and competition.

Yvonne Tay, John Rinn, Pier Paolo Pandolfi (2014)

Recent reports have described an intricate interplay among diverse RNA species, including protein-coding messenger RNAs and non-coding RNAs such as long non-coding RNAs, pseudogenes and circular RNAs. These RNA transcripts act as competing endogenous RNAs (ceRNAs) or natural microRNA sponges - they communicate with and co-regulate each other by competing for binding to shared microRNAs, a family of small non-coding RNAs that are important post-transcriptional regulators of gene expression. Understanding this novel RNA crosstalk will lead to significant insight into gene regulatory networks and have implications in human development and disease.

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Author and article information

Contributors

Milad Ashrafizadeh: milad.ashrafizadeh@sabanciuniv.edu

Alan Prem Kumar:

ORCID: http://orcid.org/0000-0002-3754-5712

apkumar@nus.edu.sg

Yuzhuo Wang:

ORCID: https://orcid.org/0000-0002-9749-8591

yuzhuo.wang@ubc.ca , ywang@bccrc.ca

Journal

Journal ID (nlm-ta): J Exp Clin Cancer Res

Journal ID (iso-abbrev): J Exp Clin Cancer Res

Title: Journal of Experimental & Clinical Cancer Research : CR

Publisher: BioMed Central (London )

ISSN (Print): 0392-9078

ISSN (Electronic): 1756-9966

Publication date (Electronic): 1 July 2022

Publication date PMC-release: 1 July 2022

Publication date Collection: 2022

Volume: 41

Electronic Location Identifier: 214

Affiliations

[1 ]GRID grid.472472.0, ISNI 0000 0004 1756 1816, Department of Biology, Faculty of Science, , Islamic Azad University, Science and Research Branch, ; Tehran, Iran

[2 ]GRID grid.411463.5, ISNI 0000 0001 0706 2472, Department of Genetics, Faculty of Advanced Science and Technology, , Tehran Medical Sciences, Islamic Azad University, ; Tehran, Iran

[3 ]GRID grid.411463.5, ISNI 0000 0001 0706 2472, Farhikhtegan Medical Convergence sciences Research Center, , Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, ; Tehran, Iran

[4 ]GRID grid.4280.e, ISNI 0000 0001 2180 6431, Department of Pharmacology, , Yong Loo Lin School of Medicine, National University of Singapore, ; Singapore, 117600 Singapore

[5 ]GRID grid.4280.e, ISNI 0000 0001 2180 6431, NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, , National University of Singapore, ; 180554 Singapore, Singapore

[6 ]GRID grid.472315.6, ISNI 0000 0004 0494 0825, Faculty of Veterinary Medicine, Kazerun Branch, , Islamic Azad University, ; Kazerun, Iran

[7 ]GRID grid.46072.37, ISNI 0000 0004 0612 7950, Department of Food Hygiene and Quality Control, Division of epidemiology & Zoonoses, , Faculty of Veterinary Medicine, University of Tehran, ; Tehran, Iran

[8 ]GRID grid.10837.3d, ISNI 0000 0000 9606 9301, School of Life, Health & Chemical Sciences, , The Open University, ; Milton Keynes, United Kingdom

[9 ]Pathology, Sheffield Teaching Hospital, Sheffield, United Kingdom

[10 ]GRID grid.508740.e, ISNI 0000 0004 5936 1556, Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, , Istinye University, ; 34396 Istanbul, Turkey

[11 ]GRID grid.17091.3e, ISNI 0000 0001 2288 9830, Department of Urologic Sciences and Vancouver Prostate Centre, , University of British Columbia, ; V6H3Z6, Vancouver, BC Canada

[12 ]GRID grid.49100.3c, ISNI 0000 0001 0742 4007, Department of Materials Science and Engineering, , Pohang University of Science and Technology (POSTECH), ; 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673 Korea

[13 ]GRID grid.1004.5, ISNI 0000 0001 2158 5405, School of Engineering, Macquarie University, ; Sydney, New South Wales 2109 Australia

[14 ]GRID grid.411950.8, ISNI 0000 0004 0611 9280, Department of Tissue Engineering and Biomaterials, , School of Advanced Medical Sciences and Technologies, Hamadan University of Medical Sciences, ; Hamadan, 6517838736 Iran

[15 ]GRID grid.54549.39, ISNI 0000 0004 0369 4060, School of Resources and Environment, , University of Electronic Science and Technology of China, ; P.O. Box 611731, Xiyuan Ave, Chengdu, PR China

[16 ]GRID grid.449416.a, ISNI 0000 0004 7433 8899, Department of Chemical Engineering, , Quchan University of Technology, ; Quchan, Iran

[17 ]GRID grid.412988.e, ISNI 0000 0001 0109 131X, Department of Chemical Sciences, , University of Johannesburg, ; Doornfontein Campus, Johannesburg, 2028 South Africa

[18 ]GRID grid.5334.1, ISNI 0000 0004 0637 1566, Faculty of Engineering and Natural Sciences, , Sabanci University, ; Orta Mahalle, Üniversite Caddesi No. 27, Orhanlı, Tuzla, 34956 Istanbul, Turkey

Author information

Alan Prem Kumar http://orcid.org/0000-0002-3754-5712

Yuzhuo Wang https://orcid.org/0000-0002-9749-8591

Article

Publisher ID: 2406

DOI: 10.1186/s13046-022-02406-1

PMC ID: 9248128

PubMed ID: 35773731

SO-VID: 51525bcc-2492-4191-a715-35961c0cd6c2

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 22 February 2022

Date accepted : 27 May 2022

Funding

Funded by: Ministry of Education (SG)

Award ID: MOE-T2EP30120-0016

Award Recipient : Alan Prem Kumar

Funded by: FundRef http://dx.doi.org/10.13039/501100004376, Terry Fox Research Institute;

Award ID: 1062

Award Recipient : Yuzhuo Wang

Funded by: FundRef http://dx.doi.org/10.13039/100009325, Canadian Health Services Research Foundation;

Award ID: 173338

Award Recipient : Yuzhuo Wang

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: prostate cancer,long non-coding rna (lncrna),microrna,drug resistance,immune evasion,exosome

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: prostate cancer, long non-coding rna (lncrna), microrna, drug resistance, immune evasion, exosome

Molecular Landscape of LncRNAs in Prostate Cancer: A focus on pathways and therapeutic targets for intervention

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Abstract

Background

Aim of review

Key scientific concepts of review

Related collections

Karger: Oncology

Most cited references 299

Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy.

The multilayered complexity of ceRNA crosstalk and competition.

Author and article information

Contributors

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Affiliations

Author information

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