Mesenchymal stem cells with Sirt1 overexpression suppress breast tumor growth via chemokine-dependent natural killer cells recruitment

Yu, Yang; Liu, Yan; Zong, Chen; Yu, Qingbo; Yang, Xue; Liang, Lei; Ye, Fei; Nong, Li; Jia, Yuxian; Lu, Yuefeng; Han, Zhipeng

doi:10.1038/srep35998

Cited by 22 publications

(18 citation statements)

References 40 publications

(51 reference statements)

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“…SIRT1 overexpression inhibited human colon cancer cell proliferation 51 . Ectopic expression of SIRT1 in mesenchymal stem cells suppressed breast cancer growth 52 , while reduced SIRT1 levels in breast cancer cells led to increased metastasis through deacetylating Smad4 signaling 53 . According to previous studies, it remains controversial whether SIRT1 acts as an oncogene or tumor suppressor, and its specific functions may depend on diverse biological signaling.…”

Section: Discussionmentioning

confidence: 99%

A novel long non-coding RNA-PRLB acts as a tumor promoter through regulating miR-4766-5p/SIRT1 axis in breast cancer

Liang

Song

et al. 2018

Cell Death Dis

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Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in cancerous processes as either oncogenes or tumor suppressor genes. Here, we demonstrated that lncRNA-PRLB (progression-associated lncRNA in breast cancer) was upregulated in human breast cancer tissues and breast cancer cell lines. Further evaluation verified that lncRNA-PRLB was positively correlated with the extent of metastasis, and its expression was correlated with shorter survival time of breast cancer patients. We identified microRNA miR-4766-5p as an inhibitory target of lncRNA-PRLB. Both lncRNA-PRLB overexpression and miR-4766-5p knockdown could remarkably enhance cell growth, metastasis, and chemoresistance. We also determined that sirtuin 1 (SIRT1) was an inhibitory target of miR-4766-5p, and that SIRT1 was inhibited by both lncRNA-PRLB knockdown and miR-4766-5p overexpression. Significantly, we found that the promotion of cell proliferation and metastasis, the acquisition of chemoresistance, and the increased expression of SIRT1 induced by lncRNA-PRLB overexpression could be partly abrogated by ectopic expression of miR-4766-5p. Taken together, our findings indicated that lncRNA could regulate the progression and chemoresistance of breast cancer via modulating the expression levels of miR-4766-5p and SIRT1, which may have a pivotal role in breast cancer treatment and prognosis prediction.

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Section: Discussionmentioning

confidence: 99%

A novel long non-coding RNA-PRLB acts as a tumor promoter through regulating miR-4766-5p/SIRT1 axis in breast cancer

Liang

Song

et al. 2018

Cell Death Dis

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“…These cells were able to recruit and polarize monocytes more efficiently than HD-MSCs thus sustaining malignant B-cell growth. Conversely, when MSCs were transfected to overexpress an NAD-dependent deacetylase sirtuin 1 (MSCs-Sirt1), they inhibited the growth of breast and prostate carcinomas by recruiting NK cells and macrophages [ 56 ]. Interestingly, MSCs associated in pancreatic carcinoma microenvironment had an increased tumor-promoting potential in respect to MSCs obtained from normal pancreas.…”

Section: Mesenchymal Stem Cells Modulate Tumor Immune Responsementioning

confidence: 99%

Tumor-educated mesenchymal stem cells promote pro-metastatic phenotype

et al. 2017

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Multipotent mesenchymal stem cells (MSCs) are recruited into tumor microenvironment in response to multiple signals produced by cancer cells. Molecules involved in their homing to tumors are the same inflammatory mediators produced by injured tissues: chemokines, cytokines and growth factors. When MSCs arrive into the tumor microenvironment these are “educated” to have pro-metastatic behaviour. Firstly, they promote cancer immunosuppression modulating both innate and adaptive immune systems. Moreover, tumor associated-MSCs trans-differentiating into cancer-associated fibroblasts can induce epithelial-mesenchymal-transition program in tumor cells. This process determinates a more aggressive phenotype of cancer cells by increasing their motility and invasiveness and favoring their dissemination to distant sites. In addition, MSCs are involved in the formation and modelling of pre-metastatic niches creating a supportive environment for colonization of circulating tumor cells.The development of novel therapeutic approaches targeting the different functions of MSCs in promoting tumor progression as well as the mechanisms underlying their activities could enhance the efficacy of conventional and immune anti-cancer therapies.Furthermore, many studies report the use of MSCs engineered to express different genes or as vehicle to specifically deliver novel drugs to tumors exploiting their strong tropism. Importantly, this approach can enhance local therapeutic efficacy and reduce the risk of systemic side effects.

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“…Accumulating evidence indicates that SIRT1 is a key regulator of diverse life events, including life span extension, inflammation, and cancer [ 24 ]. In cancer, the role of SIRT1 is controversial since it can function as both a tumor promoter and tumor suppressor [ 25 – 27 ]. SIRT1 can deacetylate histone H4 lysine 16 (H4K16) [ 28 ], whose hypoacetylation is a hallmark of human cancer [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

SIRT1 rs3758391 polymorphism and risk of diffuse large B cell lymphoma in a Chinese population

Kan

Wang

et al. 2018

Cancer Cell Int

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BackgroundThe aim of the study was to explore the association between the SIRT1 single nucleotide polymorphism (SNP) rs3758391 and diffuse large B cell lymphoma (DLBCL) in a Chinese Han population.Methods206 patients diagnosed with DLBCL and 219 healthy individuals were recruited in the present study. The genotyping of SIRT1 rs3758391 polymorphism was detected by polymerase chain reaction–restriction fragment length polymorphism. The SIRT1 mRNA expression was detected by the Taqman real-time quantitative PCR.ResultsOur study showed that the genotype TT and allele T frequency were significantly higher in DLBCL patients than that of controls (p = 0.02 and 0.01, respectively). No statistical differences were observed between SIRT1 rs3758391 and clinical characteristics of DLBCL patients. Analysis of the polymorphism revealed an increased risk of DLBCL associated with TC and TT genotype when compared with CC genotype [odds ratio = 2.621 and 3.518, respectively; 95% confidence interval (CI) 1.249–5.501 and 1.675–7.390, respectively; p = 0.011 and 0.001, respectively]. The survival analysis indicated that the patients with C allele had higher overall survival rate than those with genotype TT (p = 0.005). Furthermore, multivariate Cox regression analysis showed that the TT genotype of SIRT1 SNP rs3758391 was an independent poor prognostic factor for DLBCL patients (p = 0.006, HR 1.981, 95% CI 1.215–3.231). The SIRT1 mRNA expression was significantly upregulated in DLBCL patients than that of controls (p < 0.001). In addition, the SIRT1 mRNA expression of TT subgroup was upregulated compared with TC/CC subgroup in DLBCL patients (p < 0.001).ConclusionThese results suggest that the SIRT1 rs3758391 polymorphism is associated with the risk and survival rate of DLBCL in Chinese Han population.

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Mesenchymal stem cells with Sirt1 overexpression suppress breast tumor growth via chemokine-dependent natural killer cells recruitment

Cited by 22 publications

References 40 publications

A novel long non-coding RNA-PRLB acts as a tumor promoter through regulating miR-4766-5p/SIRT1 axis in breast cancer

A novel long non-coding RNA-PRLB acts as a tumor promoter through regulating miR-4766-5p/SIRT1 axis in breast cancer

Tumor-educated mesenchymal stem cells promote pro-metastatic phenotype

SIRT1 rs3758391 polymorphism and risk of diffuse large B cell lymphoma in a Chinese population

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