Expression of NAMPT is associated with breast invasive ductal carcinoma development and prognosis

Zhou, Shaojie; Bi, Tie-qiang; Qin, Chunxin; Yang, Xiaoqing; Pang, K. Sandy

doi:10.3892/ol.2018.8164

Cited by 26 publications

(30 citation statements)

References 24 publications

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“…NAMPT is a family member of nicotinic acid phosphoribosyltransferase (NAPRTase). Although the functional and prognostic role of NAMPT has not been well studied in cervical cancer, it is reported to predict prognosis in breast invasive ductal carcinoma [ 33 ], glioblastoma [ 34 ] and colorectal cancer [ 35 ]. TM9SF1 plays an essential role in autophagy, and its expression is reported to have a significant role in AS associated prognosis prediction in cervical cancer patients [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of an autophagy-related gene signature for survival prediction in patients with cervical cancer

et al. 2020

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Cervical cancer is one of the most common female malignancy that occurs worldwide and is reported to cause over 300,000 deaths in 2018. Autophagy controls the survival and death of cancerous cells by regulating the degradation process of cytoplasm and cellular organelle. In the present study, the differentially expressed autophagy-related genes (ARGs) between healthy and cancerous cervical tissues (squamous cell neoplasms) were obtained using data from GTEx and The Cancer Genome Atlas (TCGA) database. The functionalities of the differentially expressed ARGs were analyzed using Gene Ontology (GO) as well as the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Next, we conducted univariate Cox regression assay and obtained 12 ARGs that were associated with the prognosis of cervical cancer patients. We carried out a multivariate Cox regression analysis and developed six ARG-related prognostic signature for the survival prediction of patients with squamous cell cervical cancer (Risk score = − 0.63*ATG3–0.42*BCL2 + 0.85*CD46–0.38*IFNG+ 0.23*NAMPT+ 0.82*TM9SF1). Following the calculation of risk score using the signature, the patients were divided into high and low-risk groups according to the median value. Kaplan-Meier curve demonstrated that patients with a high-risk score tend to have a poor prognosis (P < 0.001). The value for area under the curves corresponding to the receiver operating characteristic (ROC) was 0.740. As observed, the expression of IFNG was negatively associated with lymph node metastasis (P = 0.026), while a high-risk score was significantly associated with increased age (P = 0.008). To further validate the prognostic signature, we carried out a permutation test and confirmed the performance of the risk score. In conclusion, our study developed six ARG-related prognostic signature for patients with squamous cell cervical cancer, which might help in improving the prognostic predictions of such patients.

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Section: Discussionmentioning

confidence: 99%

Identification of an autophagy-related gene signature for survival prediction in patients with cervical cancer

et al. 2020

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“…The findings of NAD measurement revealed that miR-154 caused the attenuation of intracellular NAD via inhibition of NAMPT salvage pathway. NAMPT is an essential enzyme in NAD biosynthesis and therefore its inhibition is a plausible approach in depleting intracellular NAD (30,45). Here we showed that inhibition of NAMPT and the further decline in NAD levels leads to diminished cell viability and a prominent induction of apoptosis.…”

Section: Mir-154 Regulated Nampt By Direct Binding To Its 3′-utrmentioning

confidence: 82%

“…Significantly higher expression of NAMPT in breast cancer tissues compared with normal mammary gland tissue has been previously reported and has been shown to be related to a higher tumor growth, advanced clinical stages, increased expression of progesterone and estrogen receptors and lymph node metastasis. Meanwhile, over expression of NAMPT in patients results in poor overall or disease-free survival (21,(30)(31)(32)(33)(34)(35). Additionally, exogenous administration of recombinant NAMPT not only leads to increased cell proliferation by activation of signaling pathways, but also increases cell survival by NAD production (36,37).…”

Section: Mir-154 Regulated Nampt By Direct Binding To Its 3′-utrmentioning

confidence: 99%

“…*P<0.05, ** P<0.01, ***P<0.001.Increase of miR-154 in breast cancer cells reduced cell viabilityNAMPT is elevated in diverse human malignancies such as breast cancer. This enzyme facilitates proliferation and increases survival of cancer cells(22). In the present research, we studied the effect of miR-154 on the survival of breast cancer cells using WST-1 cell survival assay.The obtained results revealed that miR-154 mimic considerably reduced cell survival in MCF-7 (P<0.05) and MDA-MB-231 (P<0.01) cells when compared to the untreated cells; whereas, treating the cells with miR-154 inhibitor considerably enhanced cell survival in both cell lines (both P<0.01).…”

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confidence: 99%

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Down-regulation of NAMPT expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin

Bolandghamtpour¹,

Nourbakhsh²,

Mousavizadeh

et al. 2019

Preprint

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Background Nicotinamide phosphoribosyltransferase (NAMPT) acts as an important enzyme in the salvage pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis. Deregulation of NAD could be associated with progression of many cancers including breast cancer. Here, we evaluated the effect of NAMPT inhibition via miR-154 on survival of breast cancer cells. Methods Breast cancer cell lines including MCF-7 and MDA-MB-231 were transfected with miR-154-5p mimic, inhibitor and their negative controls. Using real-time PCR and western blotting techniques the expression levels of NAMPT and miR-154 were determined and compared with the untreated cells. NAD levels were measured by an enzymatic method. Subsequently, colorimetric methods and flow cytometry were performed to evaluate cell viability and apoptosis. Bioinformatics analyses were performed to investigate whether NAMPT 3′-UTR is a direct target of miR-154 and the findings were confirmed by luciferase reporter assay. Results According to the obtained results, NAMPT 3′-UTR was identified as a direct target of miR-154 and the levels of this miRNA was inversely associated with NAMPT expression both at mRNA and protein levels in breast cancer cell lines. Functionally, miR-154 inhibited the NAD salvage pathway leading to a remarkable decrease in cell survival and induction of apoptosis. Co-treatment of breast cancer cells with doxorubicin and miR-154 mimic significantly reduced cell viability compared to treatment with doxorubicin alone in both cell lines. Conclusions Hence, it was concluded that the inhibition of NAD production by miR-154 might be introduced as a promising therapeutic strategy for the treatment of breast cancer either alone or in combination with other conventional chemotherapeutic agents.

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“…Although the functional and prognostic role of NAMPT has not been well studied in cervical cancer, it is reported to predict prognosis in breast invasive ductal carcinoma [33], glioblastoma [34] and colorectal cancer [35]. TM9SF1 plays an essential role in autophagy, and its expression is reported to have a significant role in AS associated prognosis prediction in cervical cancer patients [36].…”

Section: Discussionmentioning

confidence: 99%

Identification of an autophagy-related gene signature for survival prediction in patients with cervical cancer

Chen

Deng

Wang

et al. 2020

Preprint

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Autophagy controls the survival and death of cancerous cells by regulating the degradation process of cytoplasm and cellular organelle. In the present study, the differentially expressed autophagy-related genes (ARGs) between healthy and cancerous cervical tissues (squamous cell neoplasms) were obtained using data from GTEx and The Cancer Genome Atlas (TCGA) database. The functionalities of the differentially expressed ARGs were analyzed using GO and KEGG database. After univariate and multivariate cox regression assay, we got a six ARG-related prognostic signature for the survival prediction of patients with squamous cell cervical cancer (Risk score= -0.63*ATG3-0.42*BCL2+0.85*CD46-0.38*IFNG+0.23*NAMPT+0.82*TM9SF1). Kaplan-Meier curve demonstrated that patients with a high-risk score tend to have a poor prognosis (P<0.001). The value for area under the curves corresponding to the receiver operating characteristic (ROC) was 0.740. As observed, the expression of IFNG was negatively associated with lymph node metastasis (P=0.026), while a high-risk score was significantly associated with increased age (P=0.008). To further validate the prognostic signature, we carried out a permutation test and confirmed the performance of the risk score.

show abstract

Expression of NAMPT is associated with breast invasive ductal carcinoma development and prognosis

Cited by 26 publications

References 24 publications

Identification of an autophagy-related gene signature for survival prediction in patients with cervical cancer

Identification of an autophagy-related gene signature for survival prediction in patients with cervical cancer

Down-regulation of NAMPT expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin

Identification of an autophagy-related gene signature for survival prediction in patients with cervical cancer

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