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


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.


Chemosensitization Non-coding RNA Nutraceutical Therapy Tumor 



Three prime untranslated region


Acquired immunodeficiency syndrome


AKT8 virus oncogene cellular homolog


Acute lymphoblastic leukemia


Antisense non-coding RNA in the INK4 locus


Antisense oligonucleotides


Breast cancer resistance protein


Bcl-2-interacting killer


CRISPR-associated protein 9


Cancer susceptibility candidate 2


Cyclin-dependent kinase 6


Clustered regularly interspaced short palindromic repeats


Copper transporter 1


Deoxyribo nucleic acid


Double-stranded deoxyribonucleic acid


Epigallocatechin gallate


Eukaryotic translation initiation factor 4A3


Epithelial-to-mesenchymal transition


Estrogen receptor α


Fibroblast-like synoviocytes


Glyceraldehyde 3-phosphate dehydrogenase


Growth arrest-specific 5


Guanylate cyclase 2G homolog pseudogene


H2A histone family member Y


H2B histone family member X pseudogene


Histone H3 lysine 4


High-fat diet


3-Hydroxy-3-methylglutaryl-coenzyme A reductase


HOX transcript antisense intergenic RNA


Interleukin 6


Insulin-induced gene 1


Janus kinase


Long intergenic non-protein-coding RNA


Long intergenic non-protein-coding RNA p53 induced transcript


Long non-coding RNA


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


Monocyte chemoattractant protein-1


Multidrug resistance protein 1/P-glycoprotein 1


Human maternally expressed gene 3


MicroRNA155 host gene




Messenger RNA


Multidrug resistance-associated protein


Mammalian target of rapamycin


Nonalcoholic fatty liver disease


Nuclear paraspeckle assembly transcript 1


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


Nuclear factor erythroid 2-related factor 2


Non-small-cell lung carcinoma


Promoter of CDKN1A antisense DNA damage-activated RNA


Pyruvate dehydrogenase kinase 4


Phosphoinositide 3-kinase


p53 up-regulated modulator of apoptosis


Plasmacytoma variant translocation gene


Rheumatoid arthritis

RNA pol II

RNA polymerase II


Ribo nucleic acid


RNA interference


Regulator of reprogramming


ST7 antisense RNA 1


Signal transducer and activator of transcription


Transglutaminase 2


Transmembrane protein 25


Tumor necrosis factor alpha


Tumor nodes and metastasis


Taurine-up-regulated gene 1


Tumor suppressor candidate 7


Zinc finger and BTB domain-containing protein 20


Zinc-finger E-box-binding homeobox 1


ZNFX1 antisense RNA 1



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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