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

The nuclear factor-kappaB (NF-xB) signaling pathway is considered as a potential therapeutic target in cancer therapy. It has been well established that transcription factor NF-xB is involved in regulating physiological and pathological events including inflammation, immune response and differentiation. Increasing evidences suggest that deregulated NF-xB 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-xB signaling pathway under different settings. MicroRNAs (miRNAs) can dually inhibit/induce NF-xB 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-xB 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-xB activation and the progression of cancers. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) can also effectively modulate NF-xB signaling thus affecting tumorigenesis. It is noteworthy that several studies have demonstrated that lncRNAs and circRNAs can affect miRNAs in targeting NF-xB activation. They can act as competing endogenous RNA (ceRNA) thereby reducing miRNA expression to induce NFxB activation that can in turn promote cancer progression and malignancy.