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      Long non-coding RNAs modulate tumor microenvironment to promote metastasis: novel avenue for therapeutic intervention

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          Abstract

          Cancer is a devastating disease and the primary cause of morbidity and mortality worldwide, with cancer metastasis responsible for 90% of cancer-related deaths. Cancer metastasis is a multistep process characterized by spreading of cancer cells from the primary tumor and acquiring molecular and phenotypic changes that enable them to expand and colonize in distant organs. Despite recent advancements, the underlying molecular mechanism(s) of cancer metastasis is limited and requires further exploration. In addition to genetic alterations, epigenetic changes have been demonstrated to play an important role in the development of cancer metastasis. Long non-coding RNAs (lncRNAs) are considered one of the most critical epigenetic regulators. By regulating signaling pathways and acting as decoys, guides, and scaffolds, they modulate key molecules in every step of cancer metastasis such as dissemination of carcinoma cells, intravascular transit, and metastatic colonization. Gaining a good knowledge of the detailed molecular basis underlying lncRNAs regulating cancer metastasis may provide previously unknown therapeutic and diagnostic lncRNAs for patients with metastatic disease. In this review, we concentrate on the molecular mechanisms underlying lncRNAs in the regulation of cancer metastasis, the cross-talk with metabolic reprogramming, modulating cancer cell anoikis resistance, influencing metastatic microenvironment, and the interaction with pre-metastatic niche formation. In addition, we also discuss the clinical utility and therapeutic potential of lncRNAs for cancer treatment. Finally, we also represent areas for future research in this rapidly developing field.

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Hallmarks of Cancer: The Next Generation

            The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Cancer statistics, 2023

              Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries and mortality data collected by the National Center for Health Statistics. In 2023, 1,958,310 new cancer cases and 609,820 cancer deaths are projected to occur in the United States. Cancer incidence increased for prostate cancer by 3% annually from 2014 through 2019 after two decades of decline, translating to an additional 99,000 new cases; otherwise, however, incidence trends were more favorable in men compared to women. For example, lung cancer in women decreased at one half the pace of men (1.1% vs. 2.6% annually) from 2015 through 2019, and breast and uterine corpus cancers continued to increase, as did liver cancer and melanoma, both of which stabilized in men aged 50 years and older and declined in younger men. However, a 65% drop in cervical cancer incidence during 2012 through 2019 among women in their early 20s, the first cohort to receive the human papillomavirus vaccine, foreshadows steep reductions in the burden of human papillomavirus-associated cancers, the majority of which occur in women. Despite the pandemic, and in contrast with other leading causes of death, the cancer death rate continued to decline from 2019 to 2020 (by 1.5%), contributing to a 33% overall reduction since 1991 and an estimated 3.8 million deaths averted. This progress increasingly reflects advances in treatment, which are particularly evident in the rapid declines in mortality (approximately 2% annually during 2016 through 2020) for leukemia, melanoma, and kidney cancer, despite stable/increasing incidence, and accelerated declines for lung cancer. In summary, although cancer mortality rates continue to decline, future progress may be attenuated by rising incidence for breast, prostate, and uterine corpus cancers, which also happen to have the largest racial disparities in mortality.
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                Author and article information

                Contributors
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                13 June 2023
                2023
                : 11
                : 1164301
                Affiliations
                [1] 1 Watson-Crick Centre for Molecular Medicine , Islamic University of Science and Technology , Awantipora, Kashmir, India
                [2] 2 Department of Microbiology , Sher-I-Kashmir Institute of Medical Science (SKIMS) , Soura, Kashmir, India
                [3] 3 Department of Medical Lab Technology , Prince Fahd Bin Sultan Research Chair Faculty of Applied Medical Sciences , University of Tabuk , Tabuk, Saudi Arabia
                [4] 4 Department of Biochemistry , Faculty of Science , University of Tabuk , Tabuk, Saudi Arabia
                [5] 5 Department of Chemistry , Faculty of Science , University of Tabuk , Tabuk, Saudi Arabia
                [6] 6 Human Immunology Department , Research Branch , Sidra Medicine , Doha, Qatar
                [7] 7 Department of Human Genetics-Precision Medicine in Diabetes, Obesity, and Cancer Program , Sidra Medicine , Doha, Qatar
                Author notes

                Edited by: Samikshan Dutta, University of Nebraska Medical Center, United States

                Reviewed by: Shailendra Kumar Maurya, University of Nebraska Medical Center, United States

                Erika Zambalde, State University of Campinas, Brazil

                Article
                1164301
                10.3389/fcell.2023.1164301
                10299194
                37384249
                4b59e267-a897-4e46-bd0d-592b344049a7
                Copyright © 2023 Baba, Baba, Mir, Elfaki, Algehainy, Ullah, Barnawi, Altemani, Alanazi, Mustafa, Masoodi, Akil, Bhat and Macha.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 12 February 2023
                : 22 May 2023
                Funding
                Funded by: Department of Biotechnology, Ministry of Science and Technology, India , doi 10.13039/501100001407;
                Funded by: Science and Engineering Research Board , doi 10.13039/501100001843;
                This study was supported by the Ramalingaswami Re-entry Fellowship (Grant number: D.O. NO.BT/HRD/35/02/2006) from the Department of Biotechnology, Govt. of India, New Delhi, and Core Research Grant (CRG/2021/003805) from the Science and Engineering Research Board (SERB), Govt. of India, New Delhi, to MM. Promotion of University Research and Scientific Excellence (SR/PURSE/2022/121) grant from the Department of Biotechnology, Govt. of India, New Delhi to the Islamic University of Science and Technology (IUST), Awantipora, Kashmir.
                Categories
                Cell and Developmental Biology
                Review
                Custom metadata
                Cancer Cell Biology

                cancer,metastasis,long non-coding rnas,tumor microenvironment,anoikis resistance,metabolic reprogramming,immune modulation

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