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
Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran.
Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, 34956, Istanbul, Turkey.
Cancer Lett. 2021 Jul 1;509:63-80. doi: 10.1016/j.canlet.2021.03.025. Epub 2021 Apr 7.
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.
核因子-κB（NF-κB）信号通路被认为是癌症治疗中的一个潜在治疗靶点。转录因子NF-κB参与调节包括炎症、免疫反应和分化在内的生理和病理过程，这一点已经得到充分证实。越来越多的证据表明，失调的NF-κB信号传导可增强癌细胞的增殖、转移，并介导放疗和化疗耐药。相反，人们发现非编码RNA（ncRNA）在不同情况下可调节NF-κB信号通路。微小RNA（miRNA）可双重抑制/诱导NF-κB信号传导，从而影响癌细胞的生长和迁移。此外，miRNA也可能调节癌细胞对放疗和化疗的反应。miRNA对NF-κB的调节可能通过与3'-非翻译区（3'-UTR）结合来介导。有趣的是，抗肿瘤化合物在抑制NF-κB激活和癌症进展过程中可增加肿瘤抑制性miRNA的表达。长链非编码RNA（lncRNA）和环状RNA（circRNA）也可有效调节NF-κB信号传导，从而影响肿瘤发生。值得注意的是，多项研究表明lncRNA和circRNA在靶向NF-κB激活过程中可影响miRNA。它们可作为竞争性内源性RNA（ceRNA），从而降低miRNA表达以诱导NF-κB激活，进而促进癌症进展和恶性程度。
