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Interplay between JAK/STAT pathway and non-coding RNAs in different cancers

Ammad Ahmad Farooqi1, Abay M Shepetov2, Venera Rakhmetova3

  • 1Department of Molecular Oncology, Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan.

Non-Coding RNA Research
|July 18, 2024
PubMed

Insights

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is crucial in cancer progression and immune response modulation. Non-coding RNAs significantly regulate this pathway, impacting tumor microenvironment and metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is a key signaling cascade implicated in carcinogenesis and metastasis.
  • Deregulation of JAK/STAT signaling influences tumor microenvironment and immune responses.
  • The interplay between JAK/STAT signaling and non-coding RNAs (ncRNAs) is increasingly recognized for its role in cancer progression.

Purpose of the Study:

  • To review the regulation of the JAK/STAT pathway by microRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in primary and metastatic tumors.
  • To highlight the role of JAK/STAT signaling in cancer metastasis and immune cell modulation.
  • To identify knowledge gaps and advocate for the clinical translation of ncRNAs in cancer therapy.

Main Methods:

  • Literature review focusing on JAK/STAT pathway, non-coding RNAs, and cancer.
  • Analysis of mechanistic insights into STAT-signaling in macrophage polarization and immune cell infiltration.
  • Synthesis of current knowledge on ncRNA regulation of JAK/STAT in different cancer stages.

Main Results:

  • JAK/STAT signaling drives cancer metastasis and reshapes the tumor microenvironment.
  • STAT-signaling promotes M2 macrophage polarization, contributing to disease aggressiveness.
  • JAK/STAT pathway activity is modulated by ncRNAs, influencing immune cell infiltration (e.g., NK, CD4/CD8 cells) via PD-L1/PD-1 signaling.

Conclusions:

  • The JAK/STAT pathway is a central regulator of cancer progression and immune evasion.
  • MicroRNAs, lncRNAs, and circRNAs represent critical regulatory elements of the JAK/STAT pathway in cancer.
  • Further research is needed to bridge knowledge gaps and translate findings on lncRNAs and circRNAs into clinical applications for cancer treatment.

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