Evidence for the Involvement of the Master Transcription Factor NF-κB in Cancer Initiation and Progression

Puar, Yu Rou; Shanmugam, Muthu K.; Fan, Li; Arfuso, Frank; Sethi, Gautam; Tergaonkar, Vinay

doi:10.3390/biomedicines6030082

Cited by 168 publications

(124 citation statements)

References 199 publications

(278 reference statements)

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“…It has been widely reported that lncRNAs are potential crucial regulators of inflammatory signaling, including NF-κB pathway [31]. NF-κB is a significant contributor to initiation and progression of various cancers via controlling tumor cell proliferation, survival, migration, inflammation, invasion and angiogenesis [32]. Also, NF-κB pathway was reported to facilitate ESCC cell proliferation and invasion [33].…”

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confidence: 99%

ZFPM2-AS1 facilitates cell growth in esophageal squamous cell carcinoma via up-regulating TRAF4

Sun

2020

Bioscience Reports

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Emerging evidence has confirmed that long noncoding RNAs (lncRNAs) are strongly involved in tumor initiation and development. LncRNA ZFPM2 antisense RNA 1 (ZFPM2-AS1) has been identified as a tumor facilitator in some cancers; nevertheless, its functional significance and regulatory mechanism remain greatly unclear in esophageal squamous cell carcinoma (ESCC). Here, we detected ZFPM2-AS1 expression in ESCC cell lines using qRT-PCR. ZFPM2-AS1 knockdown models were established for investigating the biological function of ZFPM2-AS1 in ESCC cells. The association between miR-3612 and ZFPM2-AS1 or TRAF4 was assessed by RNA pull-down and luciferase reporter assays. The present study indicated that ZFPM2-AS1 was significantly up-regulated in ESCC cells. Functional assays manifested that ZFPM2-AS1 knockdown restrained cell proliferation, migration and invasion, and facilitated cell apoptosis in ESCC. Mechanistically, ZFPM2-AS1 promoted ESCC cell growth and up-regulated TRAF4 to trigger NF-κB pathway by sequestering miR-3612. Besides, miR-3612 was confirmed to be a tumor inhibitor in ESCC. Through restoration experiments, we observed that TRAF4 overexpression could recover the suppressive effect of ZFPM2-AS1 on ESCC cell growth. Collectively, all the results suggested that ZFPM2-AS1 was an oncogene in ESCC cell growth by up-regulating TRAF4 and activating NF-κB pathway.

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ZFPM2-AS1 facilitates cell growth in esophageal squamous cell carcinoma via up-regulating TRAF4

Sun

2020

Bioscience Reports

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“…Previous studies also suggest that ACHP exhibited cytotoxicity in adult T-cell leukemia and multiple myeloma cells by interfering with NF-κB signaling [65,67]. The activation of NF-κB, in addition to controlling tumorigenesis [68][69][70][71][72], plays a key role in the induction of fibrosis and ACHP displayed strong antifibrotic effects by suppressing the TGFβ1-induced differentiation of fibroblasts into myofibroblasts and collagen synthesis [73]. Recently, ACHP has been reported to block NF-κB signaling in mouse and human keratinocytes and inhibit multiple sources of cutaneous inflammation in mouse skin [74].…”

Section: Discussionmentioning

confidence: 97%

The IκB Kinase Inhibitor ACHP Targets the STAT3 Signaling Pathway in Human Non-Small Cell Lung Carcinoma Cells

et al. 2019

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STAT3 is an oncogenic transcription factor that regulates the expression of genes which are involved in malignant transformation. Aberrant activation of STAT3 has been observed in a wide range of human malignancies and its role in negative prognosis is well-documented.In this report, we performed high-throughput virtual screening in search of STAT3 signaling inhibitors using a cheminformatics platform and identified 2-Amino-6-[2-(Cyclopropylmethoxy)-6-Hydroxyphenyl]-4-Piperidin-4-yl Nicotinonitrile (ACHP) as the inhibitor of the STAT3 signaling pathway. The predicted hit was evaluated in non-small cell lung cancer (NSCLC) cell lines for its STAT3 inhibitory activity. In vitro experiments suggested that ACHP decreased the cell viability and inhibited the phosphorylation of STAT3 on Tyr705 of NSCLC cells. In addition, ACHP imparted inhibitory activity on the constitutive activation of upstream protein tyrosine kinases, including JAK1, JAK2, and Src. ACHP decreased the nuclear translocation of STAT3 and downregulated its DNA binding ability. Apoptosis was evidenced by cleavage of caspase-3 and PARP with the subsequent decline in antiapoptotic proteins, including Bcl-2, Bcl-xl, and survivin. Overall, we report that ACHP can act as a potent STAT3 signaling inhibitor in NSCLC cell lines.

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“…The major molecular target affected by butein treatment in most of the diseases investigated is the transcription factor nuclear factor κB (NF-κB) (Padmavathi et al, 2017). Over the last decade, NF-κB became a major target in drug discovery due to its key role in cancer development, cell proliferation and survival, inflammation, and immune responses (Ahn et al, 2007;Sethi et al, 2008;Sethi et al, 2009;Orlikova et al, 2012;Sethi et al, 2012;Shin et al, 2014;Li et al, 2015b;Monisha et al,2016;Monisha et al, 2017;Ningegowda et al, 2017;Pires et al, 2018;Mohan et al, 2018;Puar et al, 2018). Hence, in this study we aimed to evaluate the effect of butein on NF-κB and its regulated gene products in OSCC cells.…”

Section: Introductionmentioning

confidence: 99%

An Investigation on the Therapeutic Potential of Butein, A Tretrahydroxychalcone Against Human Oral Squamous Cell Carcinoma

Bordoloi

Monisha

Roy

et al. 2019

Asian Pac J Cancer Prev

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Background: Oral squamous cell carcinoma (OSCC) is one of the most predominant cancers in India. With advances in the field of oncology, a number of therapies have emerged; however, they are minimally effective. Consequently, there is a need to develop safe and effective regimens for the treatment of OSCC. Butein, a tetrahydroxychalcone has been found to exhibit potent antioxidant, anti-inflammatory, and also anti-tumor effects against several cancer types. However, its effect on OSCC is not studied yet. Methods: The effect of butein on the viability, apoptosis, migration and invasion of OSCC cells was evaluated using MTT, colony formation, PI/FACS, live and dead, scratch wound healing, and matrigel invasion assays. Further Western blot analysis was done to evaluate the expression of different proteins involved in the regulation of cancer hallmarks. Results: This is the first report exemplifying the anti-cancer effect of butein against OSCC. Our results showed that butein exhibited potent anti-proliferative, cytotoxic, anti-migratory, and anti-invasive effects in OSCC cells. It suppressed the expression of NF-κB and NF-κB-regulated gene products such as COX-2, survivin and MMP-9 which are involved in the regulation of different processes like proliferation, survival, invasion, and metastasis of OSCC cells. Conclusion Collectively, these results suggest that butein has immense potential in the management of OSCC. Nonetheless, in vivo validation is critical before moving to clinical trials.

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Evidence for the Involvement of the Master Transcription Factor NF-κB in Cancer Initiation and Progression

Cited by 168 publications

References 199 publications

ZFPM2-AS1 facilitates cell growth in esophageal squamous cell carcinoma via up-regulating TRAF4

ZFPM2-AS1 facilitates cell growth in esophageal squamous cell carcinoma via up-regulating TRAF4

The IκB Kinase Inhibitor ACHP Targets the STAT3 Signaling Pathway in Human Non-Small Cell Lung Carcinoma Cells

An Investigation on the Therapeutic Potential of Butein, A Tretrahydroxychalcone Against Human Oral Squamous Cell Carcinoma

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