Regulation of Nuclear Factor-KappaB (NF-κB) signaling pathway by non-coding RNAs in cancer: Inhibiting or promoting carcinogenesis?
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Updated: Nov 9, 2025

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Published on: May 30, 2025
Sepideh Mirzaei1, Ali Zarrabi2, Farid Hashemi3
1Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran.
Abstract:
The nuclear factor-kappaB (NF-κB) signaling pathway is considered as a potential therapeutic target in cancer therapy. It has been well established that transcription factor NF-κB is involved in regulating physiological and pathological events including inflammation, immune response and differentiation. Increasing evidences suggest that deregulated NF-κB signaling can enhance cancer cell proliferation, metastasis and also mediate radio-as well as chemo-resistance. On the contrary, non-coding RNAs (ncRNAs) have been found to modulate NF-κB signaling pathway under different settings. MicroRNAs (miRNAs) can dually inhibit/induce NF-κB signaling thereby affecting the growth and migration of cancer cells. Furthermore, the response of cancer cells to radiotherapy and chemotherapy may also be regulated by miRNAs. Regulation of NF-κB by miRNAs may be mediated via binding to 3/-UTR region. Interestingly, anti-tumor compounds can increase the expression of tumor-suppressor miRNAs in inhibiting NF-κB activation and the progression of cancers. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) can also effectively modulate NF-κB signaling thus affecting tumorigenesis. It is noteworthy that several studies have demonstrated that lncRNAs and circRNAs can affect miRNAs in targeting NF-κB activation. They can act as competing endogenous RNA (ceRNA) thereby reducing miRNA expression to induce NF-κB activation that can in turn promote cancer progression and malignancy.
Insights
Non-coding RNAs (ncRNAs) like miRNAs, lncRNAs, and circRNAs regulate the nuclear factor-kappaB (NF-κB) pathway. These ncRNAs impact cancer progression, metastasis, and therapeutic resistance by modulating NF-κB signaling.
Area of Science:
- Molecular Biology
- Cancer Biology
- Genetics
Background:
- The nuclear factor-kappaB (NF-κB) pathway is crucial in cellular processes and implicated in cancer development.
- Dysregulated NF-κB signaling promotes cancer proliferation, metastasis, and resistance to therapy.
- Non-coding RNAs (ncRNAs) are emerging regulators of cellular signaling pathways.
Purpose of the Study:
- To review the role of various ncRNAs in modulating the NF-κB signaling pathway.
- To explore how ncRNAs influence cancer cell behavior and response to treatment.
- To highlight the therapeutic potential of targeting ncRNA-NF-κB interactions in cancer.
Main Methods:
- Literature review of studies investigating ncRNAs and NF-κB signaling in cancer.
- Analysis of mechanisms by which microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) interact with NF-κB.
- Examination of the impact of these interactions on cancer progression and therapeutic outcomes.
Main Results:
- ncRNAs, including miRNAs, lncRNAs, and circRNAs, significantly modulate NF-κB activity in cancer.
- miRNAs can directly target NF-κB components or indirectly regulate it, affecting cancer cell growth and migration.
- lncRNAs and circRNAs can act as competing endogenous RNAs (ceRNAs), influencing miRNA levels and subsequently NF-κB activation, thereby impacting tumorigenesis.
Conclusions:
- ncRNAs represent key regulators of the NF-κB pathway in the context of cancer.
- Targeting ncRNA-mediated regulation of NF-κB offers promising therapeutic strategies for cancer treatment.
- Understanding these complex interactions is vital for developing novel anti-cancer therapies.
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