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Targeting Transient Receptor Potential Channels by MicroRNAs Drives Tumor Development and Progression

  • Giorgio SantoniEmail author
  • Maria Beatrice Morelli
  • Matteo Santoni
  • Massimo Nabissi
  • Oliviero Marinelli
  • Consuelo Amantini
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1131)

Abstract

Transient receptor potential (TRP) cation channel superfamily plays important roles in a variety of cellular processes such polymodal cellular sensing, adhesion, polarity, proliferation, differentiation and apoptosis. The expression of TRP channels is strictly regulated and their de-regulation can stimulate cancer development and progression.

In human cancers, specific miRNAs are expressed in different tissues, and changes in the regulation of gene expression mediated by specific miRNAs have been associated with carcinogenesis. Several miRNAs/TRP channel pairs have been reported to play an important role in tumor biology. Thus, the TRPM1 gene regulates melanocyte/melanoma behaviour via TRPM1 and microRNA-211 transcripts. Both miR-211 and TRPM1 proteins are regulated through microphthalmia-associated transcription factor (MIFT) and the expression of miR-211 is decreased during melanoma progression. Melanocyte phenotype and melanoma behaviour strictly depend on dual TRPM1 activity, with loss of TRPM1 protein promoting melanoma aggressiveness and miR-211 expression supporting tumour suppressor. TRPM3 plays a major role in the development and progression of human clear cell renal cell carcinoma (ccRCC) with von Hippel-Lindau (VHL) loss. TRPM3, a direct target of miR-204, is enhanced in ccRCC with inactivated or deleted VHL. Loss of VHL inhibits miR-204 expression that lead to increased oncogenic autophagy. Therefore, the understanding of specific TRP channels/miRNAs molecular pathways in distinct tumors could provide a clinical rationale for target therapy in cancer.

Keywords

TRP channels miRNAs Channelopathies Tumor progression Target therapy Calcium/calcineurin signaling TRPV TRPA1 TRPP TRPM 

Abbreviations

BRAF

proto-oncogene protein B-raf

BRAFV600

BRAF harbouring somatic missense mutations at the amino acid residue V600

BRN2

POU-domain transcription factor (POU3F2)

ccRCC

human clear cell renal cell carcinoma

CRC

colorectal cancer

EC

endometrial cancer

EOC

epithelial ovarian cancer

ETS-1

erythroblastosis virus E26 oncogene homolog 1

FGR2

fibroblast growth factor receptor type 2

HCC

hepatocellular carcinoma cells

LUAD

lung adenocarcinoma

MIFT

microphthalmia-associated transcription factor

miR

MicroRNAs

mRNA

messenger RNA

MTSS1

metastasis suppressor gene 1

NCX1

Na+/Ca2+ exchanger-1

NFAT5

nuclear factor of activated T-cells 5

NFATC3

nuclear factor of activated T-cells isoform c3

NSCLC

non-small cell lung carcinoma

OC

ovarian cancer

PCa

prostate cancer

PKD

Polycystic kidney disease

pri-miRs

primary miRNAs

TrkB

Tropomyosin receptor kinase B

TRPA

Transient receptor potential ankyrin

TRPC

Transient receptor potential canonical

TRPM

Transient receptor potential melastatin

TRPP

Transient receptor potential polycystic

TRPV

Transient receptor potential vanilloid

UTR

untranslated region

VHL

von Hippel-Lindau

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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Giorgio Santoni
    • 1
    Email author
  • Maria Beatrice Morelli
    • 1
  • Matteo Santoni
    • 2
  • Massimo Nabissi
    • 1
  • Oliviero Marinelli
    • 1
    • 3
  • Consuelo Amantini
    • 3
  1. 1.School of Pharmacy, Experimental Medicine SectionUniversity of CamerinoCamerinoItaly
  2. 2.Clinic and Oncology UnitMacerata HospitalMacerataItaly
  3. 3.School of Biosciences and Veterinary MedicineUniversity of CamerinoCamerinoItaly

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