Bisindole-PBD regulates breast cancer cell proliferation via SIRT-p53 axis

Sarma, P.N.; Bag, Indira; Ramaiah, M. Janaki; Kamal, Ähmed; Bhadra, Utpal; Bhadra, Manika Pal

doi:10.1080/15384047.2015.1071731

Cited by 18 publications

(12 citation statements)

References 64 publications

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“…Ablation Akt activity could reverse high proliferation ability mediated by SIRT1. These results commonly revealed intricate connections between SIRT1 and Akt which demonstrated that the SIRT1/Akt signaling axis could significantly affect the development of breast cancer, suggesting its meaningful status in breast cancer diagnosis and treatment 29 - 31 .…”

Section: Discussionmentioning

confidence: 85%

SIRT1 promotes formation of breast cancer through modulating Akt activity

Jin¹,

Wei²,

Xu³

et al. 2018

J. Cancer

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The silent information regulation factor 1 (sirtuin Type 1, SIRT1), as a kind of NAD+ dependent class III histone deacetylation enzyme, has been found to be involved in tumor proliferation, invasion, and metastasis. The roles of SIRTl in breast cancer is multifaceted depending on its substrate from upstream or downstream signaling pathway. In this study, we sought to make clear the regulating effects of SIRT1 in breast cancer cells, and to explore the underlying mechanisms through which SIRT1 regulates breast cancer. First, our results showed that SIRT1 was significantly up-regulated in breast cancer tissues and cells, which correlated with histological grade, tumor size, as well as lymph node metastasis. Then we established SIRT1-overexpressed and SIRT1- knockdown breast cancer cell lines to investigate the functions of SIRT1 in regulating colony formation, cell proliferation, cell cycle, cell apoptosis and migration. We found that overexpression of SIRT1 significantly promoted breast cancer growth both in vitro and in vivo, whereas knockdown of SIRT1 inhibited these phenotypes. Furthermore, SIRT1 was found to interact with Akt directly, consequently promoting the activity of Akt in breast cancer cells in vitro and positively correlating with expression of Akt, P-Akt, in breast cancer tissues in vivo. Down regulation the activity of Akt partially weakened the proliferative effect mediated by SIRT1. Taken together, our results demonstrated SIRT1's tumor promotion function and potential mechanisms in breast cancer, thus providing valuable therapeutic targets for breast cancer.

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Section: Discussionmentioning

confidence: 85%

SIRT1 promotes formation of breast cancer through modulating Akt activity

Jin¹,

Wei²,

Xu³

et al. 2018

J. Cancer

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“…While the functional roles of most of the lncRNAs in the co-expression network have not been previously studied, the mRNAs that have co-expression relationship with those lncRNAs have been previously reported to have important roles in various tumors including prostate cancer, glioma, breast cancer and squamous cell carcinoma of the lung (39, 44-45). Therefore, according to the functional roles of these mRNAs, we could prioritize the lncRNAs that might play key roles in GBM.…”

Section: Discussionmentioning

confidence: 99%

The Potential Roles of Long Noncoding RNAs (lncRNA) in Glioblastoma Development

Liu

Mitra

Zhao

et al. 2016

Molecular Cancer Therapeutics

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Long non-coding RNA (lncRNA) may contribute to the initiation and progression of tumor. In this study, we first systematically compared lncRNA and mRNA expression between GBM and paired normal brain tissues using microarray data. We found 27 lncRNA and 82 mRNA significantly up-regulated in GBM, as well as 198 lncRNA and 285 mRNA significantly down-regulated in GBM. We identified 138 co-expressed lncRNA-mRNA pairs from these differentially expressed lncRNA and genes. Subsequent pathway analysis of the lncRNA-paired genes indicated that EphrinB-EPHB, p75-mediated signaling, TNF alpha/NF-κB, and ErbB2/ErbB3 signaling pathways might be altered in GBM. Specifically, lncRNA RAMP2-AS1 had significant decrease of expression in GBM tissues and showed co-expressional relationship with NOTCH3, an important tumor promoter in many neoplastic diseases. Our follow up experiment indicated that (1) an overexpression of RAMP2-AS1 reduced GBM cell proliferation in vitro and also reduced GBM xenograft tumors in vivo; (2) NOTCH3 and RAMP2-AS1 co-expression rescued the inhibitory action of RAMP2-AS1 in glioblastoma cells; and (3) RNA pull-down assay revealed a direct interaction of RAMP2-AS1 with DHC10, which may consequently inhibit, as we hypothesize, the expression of NOTCH3 and its downstream signaling molecule HES1 in GBM. Taken together, our data revealed that lncRNA expression profile in GBM tissue was significantly altered; and RAMP2-AS1 might play a tumor suppressive role in GBM through an indirect inhibition of NOTCH3. Our results provided some insights into understanding the key roles of lncRNA-mRNA co-regulation in human GBM and the mechanisms responsible for GBM progression and pathogenesis.

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“…Since p53 and NAD are both proved to influence the energy metabolism in cancer cells and the acetylation of p53 is regulated by NAD-dependent SIRT1 deacetylase [ 9 , 25 ], the NAD metabolism may be potentially linked with p53 function in CRC tissues. As a tumor suppressor, p53 is frequently mutated in various neoplastic types during tumorigenesis [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…Nicotinamide mononucleotide adenylyl transferases (NMNATs) are rate-limiting enzymes, which catalyze the synthesis of NAD from nicotinamide mononucleotide (NMN). Three NMNAT isoforms have been identified in mammals, including NMNAT1, NMNAT2, and NMNAT3 [ 4 , 9 ]. Among the three NMNAT isoforms, NMNAT2 is reported to be most sensitive to NAD and can act as a sensor to intracellular metabolic state and high levels of NMNAT2 were detected in the organs with high energy consumption, such as heart, brain, and skeletal muscle [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Nicotinamide Mononucleotide Adenylyl Transferase 2: A Promising Diagnostic and Therapeutic Target for Colorectal Cancer

Cui

Jia

Deng

et al. 2016

BioMed Research International

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Colorectal cancer (CRC) is one of the most common cancers all over the world. It is essential to search for more effective diagnostic and therapeutic methods for CRC. Abnormal nicotinamide adenine dinucleotide (NAD) metabolism has been considered as a characteristic of cancer cells. In this study, nicotinamide mononucleotide adenylyl transferases (NMNATs) as well as p53-mediated cancer signaling pathways were investigated in patients with colorectal cancer. The CRC tissues and adjacent normal tissues were obtained from 95 untreated colorectal cancer patients and were stained for expression of nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) and p53. The survival rate was analyzed by the Kaplan-Meier method and the log-rank test. The multivariate Cox proportional hazard regression analysis was conducted as well. Our data demonstrated that expression of NMNAT2 and p53 was significantly higher in CRC tissues, while NMNAT2 expression is in correlation with the invasive depth of tumors and TNM stage. Significant positive correlation was found between the expression of NMNAT2 and the expression of p53. However, NMNAT2 expression was not a statistically significant prognostic factor for overall survival. In conclusion, our results indicated that NMNAT2 might participate in tumorigenesis of CRC in a p53-dependent manner and NMNAT2 expression might be a potential therapeutic target for CRC.

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Bisindole-PBD regulates breast cancer cell proliferation via SIRT-p53 axis

Cited by 18 publications

References 64 publications

SIRT1 promotes formation of breast cancer through modulating Akt activity

SIRT1 promotes formation of breast cancer through modulating Akt activity

The Potential Roles of Long Noncoding RNAs (lncRNA) in Glioblastoma Development

Nicotinamide Mononucleotide Adenylyl Transferase 2: A Promising Diagnostic and Therapeutic Target for Colorectal Cancer

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