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      Non-coding RNAs in lung cancer: molecular mechanisms and clinical applications

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          Abstract

          Lung cancer (LC) is a heterogeneous disease with high malignant degree, rapid growth, and early metastasis. The clinical outcomes of LC patients are generally poor due to the insufficient elucidation of pathological mechanisms, low efficiency of detection and assessment methods, and lack of individualized therapeutic strategies. Non-coding RNAs (ncRNAs), including microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA), are endogenous regulators that are widely involved in the modulation of almost all aspects of life activities, from organogenesis and aging to immunity and cancer. They commonly play vital roles in various biological processes by regulating gene expression via their interactions with DNA, RNA, or protein. An increasing amount of studies have demonstrated that ncRNAs are closely correlated with the initiation and development of LC. Their dysregulation promotes the progression of LC via distinct mechanisms, such as influencing protein activity, activating oncogenic signaling pathways, or altering specific gene expression. Furthermore, some ncRNAs present certain clinical values as biomarker candidates and therapeutic targets for LC patients. A complete understanding of their mechanisms in LC progression may be highly beneficial to developing ncRNA-based therapeutics for LC patients. This review mainly focuses on the intricate mechanisms of miRNA, lncRNA, and circRNA involved in LC progression and discuss their underlying applications in LC treatment.

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          Most cited references219

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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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            Cancer statistics, 2018

            Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2014, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2015, were collected by the National Center for Health Statistics. In 2018, 1,735,350 new cancer cases and 609,640 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2005-2014) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2006-2015) declined by about 1.5% annually in both men and women. The combined cancer death rate dropped continuously from 1991 to 2015 by a total of 26%, translating to approximately 2,378,600 fewer cancer deaths than would have been expected if death rates had remained at their peak. Of the 10 leading causes of death, only cancer declined from 2014 to 2015. In 2015, the cancer death rate was 14% higher in non-Hispanic blacks (NHBs) than non-Hispanic whites (NHWs) overall (death rate ratio [DRR], 1.14; 95% confidence interval [95% CI], 1.13-1.15), but the racial disparity was much larger for individuals aged <65 years (DRR, 1.31; 95% CI, 1.29-1.32) compared with those aged ≥65 years (DRR, 1.07; 95% CI, 1.06-1.09) and varied substantially by state. For example, the cancer death rate was lower in NHBs than NHWs in Massachusetts for all ages and in New York for individuals aged ≥65 years, whereas for those aged <65 years, it was 3 times higher in NHBs in the District of Columbia (DRR, 2.89; 95% CI, 2.16-3.91) and about 50% higher in Wisconsin (DRR, 1.78; 95% CI, 1.56-2.02), Kansas (DRR, 1.51; 95% CI, 1.25-1.81), Louisiana (DRR, 1.49; 95% CI, 1.38-1.60), Illinois (DRR, 1.48; 95% CI, 1.39-1.57), and California (DRR, 1.45; 95% CI, 1.38-1.54). Larger racial inequalities in young and middle-aged adults probably partly reflect less access to high-quality health care. CA Cancer J Clin 2018;68:7-30. © 2018 American Cancer Society.
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              Tumor microenvironment as a therapeutic target in cancer

              Tumor microenvironment denotes the non-cancerous cells and components presented in the tumor, including molecules produced and released by them. The constant interactions between tumor cells and the tumor microenvironment play decisive roles in tumor initiation, progression, metastasis, and response to therapies. The tumor microenvironment as a therapeutic target in cancer has attracted great research and clinical interest. Here we summarize the current progress in targeting the tumor microenvironment in both drug development and clinical trials; highlight challenges in targeting the tumor microenvironment to achieve therapeutic efficacy; explore new technologies and approaches to better decipher the tumor microenvironment; and discuss strategies to intervene in the pro-tumor microenvironment and maximize therapeutic benefits.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/724869Role: Role: Role:
                Role: Role:
                Role: Role:
                Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2291429Role:
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                08 September 2023
                2023
                : 13
                : 1256537
                Affiliations
                [1] 1 The Affiliated Hospital of Qingdao University , Qingdao, Shandong, China
                [2] 2 Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao Medical College, Qingdao University , Qingdao, Shandong, China
                [3] 3 School of Basic Medicine, Qingdao University , Qingdao, Shandong, China
                [4] 4 Department of Rehabilitation Medicine, the Affiliated Hospital of Qingdao University , Qingdao, Shandong, China
                Author notes

                Edited by: Catalin Marian, Victor Babes University of Medicine and Pharmacy, Romania

                Reviewed by: Patricia Silveyra, Indiana University Bloomington, United States; Azhar Ali, National University of Singapore, Singapore

                *Correspondence: Xiang Ao, xiangao2016@ 123456163.com ; Junqiang Xue, xuejq@ 123456qdu.edu.cn
                Article
                10.3389/fonc.2023.1256537
                10514911
                37746261
                e1f10a81-a1d4-454d-a5fc-2b421c7e3565
                Copyright © 2023 Liu, Ding, Wang, Ao and Xue

                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
                : 11 July 2023
                : 24 August 2023
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 219, Pages: 18, Words: 6607
                Funding
                Funded by: China Postdoctoral Science Foundation , doi 10.13039/501100002858;
                All authors are supported by Qingdao Medical College, Qingdao University. This work was funded by the China Postdoctoral Science Foundation (2018M642607).
                Categories
                Oncology
                Review
                Custom metadata
                Molecular and Cellular Oncology

                Oncology & Radiotherapy
                lung cancer,micrornas,long non-coding rnas,circular rnas,biomarker,therapeutic target

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