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

• Published in: Cancer letters 2021-07, Vol.509, p.63-80
• Main Authors: Mirzaei, Sepideh, Zarrabi, Ali, Hashemi, Farid, Zabolian, Amirhossein, Saleki, Hossein, Ranjbar, Adnan, Seyed Saleh, Seyed Hesam, Bagherian, Morteza, Sharifzadeh, Seyed omid, Hushmandi, Kiavash, Liskova, Alena, Kubatka, Peter, Makvandi, Pooyan, Tergaonkar, Vinay, Kumar, Alan Prem, Ashrafizadeh, Milad, Sethi, Gautam
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; Angiogenesis; Apoptosis; Breast cancer; Cancer; Cancer therapies; Carcinogenesis; Cell cycle; Cell migration; Cell proliferation; Chemoresistance; Chemotherapy; Circular RNA; Drug resistance; Genes; Immune response; Immunotherapy; Inflammation; Kinases; Long non-coding RNAs; Malignancy; Medical prognosis; Metastases; Metastasis; MicroRNAs; miRNA; NF-κB protein; Non-coding RNA; Nuclear factor-kappaB (NF-κB); Ovarian cancer; Phosphorylation; Physiology; Proteins; Radiation therapy; Radioresistance; RNA polymerase; Signal transduction; Tumor necrosis factor-TNF; Tumorigenesis
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2021.03.025

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. •NF-ĸB acts as a potential regulator of inflammation and is abnormal expressed in tumor cells.•Long non-coding RNAs can regulate NF-ĸB signalling by diverse mechanisms in cancer progression/inhibition.•MicroRNAs can bind to 3/-UTR of NF-ĸB to modulate its activation, and thereby affecting tumorigenesis.•Long non-coding RNAs can regulate miRNA expression that may act as upstream mediators of NF-ĸB.