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

  • Shruti Mishra
  • Sumit S. Verma
  • Vipin Rai
  • Nikee Awasthee
  • Srinivas Chava
  • Kam Man Hui
  • Alan Prem Kumar
  • Kishore B. ChallagundlaEmail author
  • Gautam SethiEmail author
  • Subash C. GuptaEmail author
Review

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.

Keywords

Chemosensitization Non-coding RNA Nutraceutical Therapy Tumor 

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

Notes

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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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Biochemistry, Institute of ScienceBanaras Hindu UniversityVaranasiIndia
  2. 2.Department of Biochemistry and Molecular Biology, and Fred & Pamela Buffett Cancer CenterUniversity of Nebraska Medical CenterOmahaUSA
  3. 3.Division of Cellular and Molecular ResearchHumphrey Oei Institute of Cancer Research, National Cancer CentreSingaporeSingapore
  4. 4.Department of Pharmacology, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore

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