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Long non-coding RNAs are emerging targets of phytochemicals for cancer and other chronic diseases

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Abstract

The long non-coding RNAs (lncRNAs) are the crucial regulators of human chronic diseases. Therefore, approaches such as antisense oligonucleotides, RNAi technology, and small molecule inhibitors have been used for the therapeutic targeting of lncRNAs. During the last decade, phytochemicals and nutraceuticals have been explored for their potential against lncRNAs. The common lncRNAs known to be modulated by phytochemicals include ROR, PVT1, HOTAIR, MALAT1, H19, MEG3, PCAT29, PANDAR, NEAT1, and GAS5. The phytochemicals such as curcumin, resveratrol, sulforaphane, berberine, EGCG, and gambogic acid have been examined against lncRNAs. In some cases, formulation of phytochemicals has also been used. The disease models where phytochemicals have been demonstrated to modulate lncRNAs expression include cancer, rheumatoid arthritis, osteoarthritis, and nonalcoholic fatty liver disease. The regulation of lncRNAs by phytochemicals can affect multi-steps of tumor development. When administered in combination with the conventional drugs, phytochemicals can also produce synergistic effects on lncRNAs leading to the sensitization of cancer cells. Phytochemicals target lncRNAs either directly or indirectly by affecting a wide variety of upstream molecules. However, the potential of phytochemicals against lncRNAs has been demonstrated mostly by preclinical studies in cancer models. How the modulation of lncRNAs by phytochemicals produce therapeutic effects on cancer and other chronic diseases is discussed in this review.

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Abbreviations

3′UTR:

Three prime untranslated region

AIDS:

Acquired immunodeficiency syndrome

AKT:

AKT8 virus oncogene cellular homolog

ALL:

Acute lymphoblastic leukemia

ANRIL:

Antisense non-coding RNA in the INK4 locus

ASOs:

Antisense oligonucleotides

BCRP:

Breast cancer resistance protein

BIK:

Bcl-2-interacting killer

CAS9:

CRISPR-associated protein 9

CASC2:

Cancer susceptibility candidate 2

CDK6:

Cyclin-dependent kinase 6

CRISPR:

Clustered regularly interspaced short palindromic repeats

CTR1:

Copper transporter 1

DNA:

Deoxyribo nucleic acid

dsDNA:

Double-stranded deoxyribonucleic acid

EGCG:

Epigallocatechin gallate

EIF4A3:

Eukaryotic translation initiation factor 4A3

EMT:

Epithelial-to-mesenchymal transition

ERα:

Estrogen receptor α

FLS:

Fibroblast-like synoviocytes

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

GAS5:

Growth arrest-specific 5

GUCY2GP:

Guanylate cyclase 2G homolog pseudogene

H2AFY:

H2A histone family member Y

H2BFXP:

H2B histone family member X pseudogene

H3K4:

Histone H3 lysine 4

HFD:

High-fat diet

HMGCR:

3-Hydroxy-3-methylglutaryl-coenzyme A reductase

HOTAIR:

HOX transcript antisense intergenic RNA

IL-6:

Interleukin 6

INSIG1:

Insulin-induced gene 1

JAK:

Janus kinase

LINC:

Long intergenic non-protein-coding RNA

linc-PINT:

Long intergenic non-protein-coding RNA p53 induced transcript

LncRNA:

Long non-coding RNA

MAP1LC3B2:

Microtubule-associated proteins 1A/1B light chain 3B

MCP-1:

Monocyte chemoattractant protein-1

MDR1/P-gp:

Multidrug resistance protein 1/P-glycoprotein 1

MEG3:

Human maternally expressed gene 3

MIR155HG:

MicroRNA155 host gene

miRNA:

MicroRNA

mRNA:

Messenger RNA

MRP:

Multidrug resistance-associated protein

mTOR:

Mammalian target of rapamycin

NAFLD:

Nonalcoholic fatty liver disease

NEAT1:

Nuclear paraspeckle assembly transcript 1

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

Nrf2:

Nuclear factor erythroid 2-related factor 2

NSCLC:

Non-small-cell lung carcinoma

PANDAR:

Promoter of CDKN1A antisense DNA damage-activated RNA

PDK4:

Pyruvate dehydrogenase kinase 4

PI3K:

Phosphoinositide 3-kinase

PUMA:

p53 up-regulated modulator of apoptosis

PVT1:

Plasmacytoma variant translocation gene

RA:

Rheumatoid arthritis

RNA pol II:

RNA polymerase II

RNA:

Ribo nucleic acid

RNAi:

RNA interference

ROR:

Regulator of reprogramming

ST7OT1:

ST7 antisense RNA 1

STAT:

Signal transducer and activator of transcription

TGM2:

Transglutaminase 2

TMEM25:

Transmembrane protein 25

TNF-α:

Tumor necrosis factor alpha

TNM:

Tumor nodes and metastasis

TUG1:

Taurine-up-regulated gene 1

TUSC7:

Tumor suppressor candidate 7

Zbtb20:

Zinc finger and BTB domain-containing protein 20

ZEB1:

Zinc-finger E-box-binding homeobox 1

ZFAS1:

ZNFX1 antisense RNA 1

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Acknowledgements

The authors would like to thank Richard Heather and Pokhrel Arya from UNMC High School Alliance Program at the University of Nebraska Medical Center, USA, for thoroughly reading the article. SCG is thankful to the Science and Engineering Research Board (ECR/2016/000034) and University Grants Commission [No.F. 30-112/2015 (BSR)] for the financial assistance. Dr. Challagundla’s laboratory is supported in whole or part from the NIH/NCI Grant (K22CA197074-01); the Nebraska State DHHS (LB506); IDeA Award from the NIH/NIGMS (P30 GM106397); UNMC Pediatric Cancer Research Center; Fred and Pamela Buffett Cancer Center’s Pilot Grant (P30 CA036727) in conjunction with the UNMC Pediatric Cancer Research Center; Leukemia Research Foundation Grant and the Department of Biochemistry and Molecular Biology start-up at UNMC. SM, SSV, and NA are supported from ICMR New Delhi (3/1/3/JRF-2016/LS/HRD-65-80388), DBT New Delhi (DBT/2017/BHU/786), and BHU Varanasi (R/Dev/IX-Sch-BHU Res Sch 2018-19), respectively.

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  1. Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India

    Shruti Mishra, Sumit S. Verma, Vipin Rai, Nikee Awasthee & Subash C. Gupta

  2. Department of Biochemistry and Molecular Biology, and Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA

    Srinivas Chava & Kishore B. Challagundla

  3. Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore, 169610, Singapore

    Kam Man Hui

  4. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore

    Alan Prem Kumar & Gautam Sethi

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Mishra, S., Verma, S.S., Rai, V. et al. Long non-coding RNAs are emerging targets of phytochemicals for cancer and other chronic diseases. Cell. Mol. Life Sci. 76, 1947–1966 (2019). https://doi.org/10.1007/s00018-019-03053-0

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