Long non-coding RNAs and exosomal lncRNAs: Potential functions in lung cancer progression, drug resistance and tumor microenvironment remodeling - 27/05/22

Doi : 10.1016/j.biopha.2022.112963

Maliheh Entezari ^a,^b,^{^{1
These authors have participated equally to manuscript preparation.}}, Maryam Ghanbarirad ^a,^b,^{^{1
These authors have participated equally to manuscript preparation.}}, Afshin Taheriazam ^b,^c,^{^{1
These authors have participated equally to manuscript preparation.}}, Mehrdokht Sadrkhanloo ^d, Amirhossein Zabolian ^e, Mohammad Ali Shekhi Beig Goharrizi ^f, Kiavash Hushmandi ^g, Amir Reza Aref ^h,ⁱ, Milad Ashrafizadeh ^j, Ali Zarrabi ^k, Noushin Nabavi ^l, Navid Rabiee ^m, Mehrdad Hashemi ^a,^b,^⁎ , Saeed Samarghandian ^n,^⁎
^a Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
^b Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
^c Department of Orthopedics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
^d Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
^e Department of Orthopedics, School of Medicine, 5th Azar Hospital, Golestan University of Medical Sciences, Golestan, Iran
^f Atherosclerosis Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
^g Department of Food Hygiene and Quality Control, Division of Epidemiology & Zoonosis, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
^h Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
ⁱ Translational Sciences, Xsphera Biosciences Inc., 6 Tide Street, Boston, MA 02210, USA
^j Faculty of Engineering and Natural Sciences, Sabanci University, Orta Mahalle, Üniversite Caddesi No. 27, Orhanlı, Tuzla, 34956 Istanbul, Turkey
^k Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Sariyer, Istanbul 34396, Turkey
^l Department of Urological Sciences and Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada V6H3Z6
^m School of Engineering, Macquarie University, Sydney, New South Wales 2109, Australia
ⁿ Healthy Ageing Research Centre, Neyshabur University of Medical Sciences, Neyshabur, Iran

^⁎Corresponding author at: Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad UniversityTehranIran^⁎⁎Corresponding author.

Abstract

Among the different kinds of tumors threatening human life, lung cancer is one that is commonly observed in both males and females. The aggressive behavior of lung cancer and interactions occurring in tumor microenvironment enhances the malignancy of this tumor. The lung tumor cells have demonstrated capacity in developing chemo- and radio-resistance. LncRNAs are a category of non-coding RNAs that do not encode proteins, but their aberrant expression is responsible for tumor development, especially lung cancer. In the present review, we focus on both lncRNAs and exosomal lncRNAs in lung cancer, and their ability in regulating proliferation and metastasis. Cell cycle progression and molecular mechanisms related to lung cancer metastasis such as EMT and MMPs are regulated by lncRNAs. LncRNAs interact with miRNAs, STAT, Wnt, EZH2, PTEN and PI3K/Akt signaling pathways to affect progression of lung cancer cells. LncRNAs demonstrate both tumor-suppressor and tumor-promoting functions in lung cancer. They can be considered as biomarkers in lung cancer and especially exosomal lncRNAs present in body fluids are potential tools for minimally invasive diagnosis. Furthermore, we discuss regulation of lncRNAs by anti-cancer drugs and genetic tools as well as the role of these factors in therapy response of lung cancer cells.

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Graphical Abstract

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Highlights

•	Lung cancer is the most malignant tumor in human.
•	Epigenetic alterations mediate lung cancer initiation and progression.
•	Abnormal Long non-coding RNA (lnc) expression results in proliferation, metastasis and therapy resistance in lung cancer.
•	Exosomal lncRNAs are potential diagnostic and prognostic tools.
•	Therapeutic targeting of lncRNAs is effective in lung cancer therapy.

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Abbreviations : SCLC, NSCLC, miRNA, lncRNA, circRNA, EMT, ncRNAs, mRNA, ceRNA, VEGFC, MDM4, PCD, EZH2, MDSCs, CCL5, CAFs, EGFR, SIRT5, CYTOR, MMPs, TH1, STAT3, NF-κB, HK2, IL-6, siRNA, shRNA, PI3K, Akt, PTEN