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STAT signaling as a target for intervention: from cancer inflammation and angiogenesis to non-coding RNAs modulation

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Abstract

As a landmark, scientific investigation in cytokine signaling and interferon-related anti-viral activity, signal transducer and activator of transcription (STAT) family of proteins was first discovered in the 1990s. Today, we know that the STAT family consists of several transcription factors which regulate various molecular and cellular processes, including proliferation, angiogenesis, and differentiation in human carcinoma. STAT family members play an active role in transducing signals from cell membrane to nucleus through intracellular signaling and thus activating gene transcription. Additionally, they are also associated with the development and progression of human cancer by facilitating inflammation, cell survival, and resistance to therapeutic responses. Accumulating evidence suggests that not all STAT proteins are associated with the progression of human malignancy; however, STAT3/5 are constitutively activated in various cancers, including multiple myeloma, lymphoma, breast cancer, prostate hepatocellular carcinoma, and non-small cell lung cancer. The present review highlights how STAT-associated events are implicated in cancer inflammation, angiogenesis and non-coding RNA (ncRNA) modulation to highlight potential intervention into carcinogenesis-related cellular processes.

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Data Availability

The datasets generated during and/or analyzed during the current study are not publicly available due to [not applicable for review articles] but are available from the corresponding author on reasonable request.

Abbreviations

AKT:

protein kinase B

Ang-2:

Angiopoietin-2

APE/Ref-1:

Apurinic (apyrimidinic) endonuclease/redox-factor 1

CPT1B:

Carnitine palmitoyltransferase 1B

CBP:

CREB binding protein

CDKN1A:

cyclin dependent kinase inhibitor 1 A

CRC:

Colorectal cancer

COX-2:

cyclooxygenase-2

DC:

dendritic cell

DBD:

DNA binding domain

DUXAP8:

double homeobox A pseudogene 8

EBV:

Epstein-Barr virus

FAO:

fatty acid beta-oxidation

GRP:

glucose-regulated protein

TDM1:

trastuzumab emtansine

HTLV-1:

human T-lymphotropic virus type 1

HOST2:

human ovarian cancer-specific transcript 2

HIC1:

hypermethylation of cancer 1

HIF-1α:

Hypoxia-inducible factor 1-alpha

IFN:

interferon

IFNAR:

interferon alpha receptor

IL:

interleukin

JAK:

Janus kinase

MLL1:

mixed lineage leukaemia protein-1

MMP:

matrix metalloproteinase

ncRNA:

non-coding RNA

NFκB:

nuclear factor kappaB

NK:

natural killer

Okt4:

octamer-binding transcription factor 4

PD-L1:

programmed death-ligand 1

PI3K:

phosphoinositide 3-kinase

PRL:

prolactin

RN/OS:

reactive nitrogen/oxygen species

SH2:

Src-homology 2 (domain)

SCLC:

small cell lung cancer

SNHG10:

small nucleolar RNA host gene 10

SOC:

suppressor of cytokine signaling

STAT TF:

transcription factor

STAT:

signal transducer and activator of transcription

TAD:

transcriptional activation domain

DBD:

DNA-binding domain

PTP:

protein tyrosine phosphatases

TGF-β:

transforming growth factor-beta

Th:

T-helper

TIMPs:

tissue inhibitors of metalloproteinases

TME:

tumor microenvironment

TNF-α:

tumour necrosis factor-alpha

TRAF:

TNF receptor-associated factor

TYK2:

tyrosine kinase 2

VEGF:

vascular endothelial growth factor

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Authors and Affiliations

  1. Department of Biotechnology, Maharishi Markandeshwar (Deemed to be University), 133 207, Mullana- Ambala, Haryana, India

    Hardeep Singh Tuli

  2. NGO Praeventio, 50407, Tartu, Estonia

    Katrin Sak

  3. Department of Pharmacology, School of Pharmaceutical Education and Research (Formerly, Faculty of Pharmacy), Jamia Hamdard (Deemed to be University), Delhi, India

    Ashif Iqubal

  4. Department of Medical Laboratory Technology, University Institute of Applied Health Sciences, Chandigarh University, Mohali, 140413, Gharuan, Punjab, India

    Vivek Kumar Garg

  5. Department of Molecular Biology and Genetics, Faculty of Science, Mugla Sitki Kocman University, TR48000, Mugla, Turkey

    Mehmet Varol

  6. Department of Zoology, Central University of Punjab, 151401, Village-Ghudda, Punjab, India

    Uttam Sharma & Aklank Jain

  7. Amity Institute of Environment Toxicology Safety and Management, Amity University, Noida, Uttar Pradesh, India

    Abhishek Chauhan

  8. Department of Pharmacology, Faculty of Pharmacy, Erciyes University, 38039, Kayseri, Turkey

    Mukerrem Betul Yerer

  9. Division of Pathology, ICAR-Indian Veterinary Research Institute, 243122, Bareilly, Uttar Pradesh, India

    Kuldeep Dhama

  10. Department of Biochemistry, Central University of Punjab, 151401, Village-Ghudda, Punjab, India

    Manju Jain

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Contributions

HST and KS designed and written; AI contributed in clinical section; VKG contributed in chemoresistance section; MV contributed in angiogenesis section; US contributed in ncRNA section; AC edited the final paper; MBY contributed in inflammation section; KD and MJ contributed to manuscript revision; AJ contributed in ncRNA section and draft reading.

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Correspondence to Hardeep Singh Tuli or Aklank Jain.

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Tuli, H.S., Sak, K., Iqubal, A. et al. STAT signaling as a target for intervention: from cancer inflammation and angiogenesis to non-coding RNAs modulation. Mol Biol Rep 49, 8987–8999 (2022). https://doi.org/10.1007/s11033-022-07399-w

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