Let-7d increases ovarian cancer cell sensitivity to a genistein analog by targeting c-Myc

Ning, Yingxia; Luo, Xin; Xu, Meng; Feng, Xiaoshan; Wang, Jian

doi:10.18632/oncotarget.20413

Cited by 20 publications

(18 citation statements)

References 34 publications

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“…Ning Y, et al, found that let-7d was downregulated in ovarian cancer tissues compared with normal ovarian tissues [22]. Let-7d was also reported to be downregulated in oral squamous cell carcinoma [33] and renal cell carcinoma [24], which was consistent with our results in breast cancer.…”

Section: Discussionsupporting

confidence: 91%

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Let-7d Inhibits Growth and Metastasis in Breast Cancer by Targeting Jab1/Cops5

Wei

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: MicroRNAs (miRNAs) regulate the expressions of cancer-related genes, and are involved in the development and progression of various human cancers. Here, we performed further analyses to determine whether let-7d is functionally linked to Jab1 in breast cancer. Methods: In situ hybridization and immunohistochemical analyses were used to determine the level of let-7d and Jab1 in breast cancer clinical specimens and its correlation with clinicopathological data. Let-7d overexpressing breast cancer cell lines combined with mouse models bearing cell-derived xenografts were used to assess the functional role of let-7d both in vitro and in vivo. Results: In this study, we found that let-7d was downregulated in breast cancer tissues, coupled with the elevations of Jab1 protein expressions, compared with paired adjacent noncancerous breast tissues. Let-7d overexpression significantly suppressed the proliferation and invasion in MCF-7 and MDA-MB-231 cells. Dual luciferase reporter assay indicated that Jab1 was the direct target of let-7d. Stepwise studies from in vitro and in vivo experiments indicated that let-7d overexpression inhibited cell growth and decreased Jab1 expressions in breast cancer cells and nude mice tumor tissues. Statistical analyses demonstrated that breast cancer patients with low levels of let-7d or high levels of Jab1 had a significant correlation with worse prognosis. Conclusion: These findings provide novel insights into molecular mechanism of let-7d and Jab1 in tumor development and progression of breast cancer, and thus let-7d/Jab1 are novel potential therapeutic targets for breast cancer patients.

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Section: Discussionsupporting

confidence: 91%

“…Let-7 family, including let-7d, was reported to inhibit tumor pathogenesis [20,22]. On the other hand, let-7d contributes to the pathogenesis of some cancers.…”

Section: Introductionmentioning

confidence: 99%

Let-7d Inhibits Growth and Metastasis in Breast Cancer by Targeting Jab1/Cops5

Wei

Liu

et al. 2018

Cell Physiol Biochem

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“…As the inhibition of PIM2 increases, expression of cMyc protein reduces in the OC cells [ 13 ]. On the other hand, recently, knocking down of cMyc caused reduction of the PI3K/AKT signaling pathway in OC cells [ 82 ] which is opposite to as reported in normal cells [ 83 ]. This data suggests the involvement of PI3K, PIM kinases and cMyc together in OC cells but further studies to probe mechanistic approach will help to understand exact relationship between them.…”

Section: Pim Kinases and Proteins Involved In Cellular Functions Omentioning

confidence: 83%

PIM Kinases and Their Relevance to the PI3K/AKT/mTOR Pathway in the Regulation of Ovarian Cancer

et al. 2018

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Ovarian cancer is a medical term that includes a number of tumors with different molecular biology, phenotypes, tumor progression, etiology, and even different diagnosis. Some specific treatments are required to address this heterogeneity of ovarian cancer, thus molecular characterization may provide an important tool for this purpose. On a molecular level, proviral-integration site for Moloney-murine leukemia virus (PIM) kinases are over expressed in ovarian cancer and play a vital role in the regulation of different proteins responsible for this tumorigenesis. Likewise, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is also a central regulator of the ovarian cancer. Interestingly, recent research has linked the PIM kinases to the PI3K/AKT/mTOR pathway in several types of cancers, but their connection in ovarian cancer has not been studied yet. Once the exact relationship of PIM kinases with the PI3K/AKT/mTOR pathway is acquired in ovarian cancer, it will hopefully provide effective treatments on a molecular level. This review mainly focuses on the role of PIM kinases in ovarian cancer and their interactions with proteins involved in its progression. In addition, this review suggests a connection between the PIM kinases and the PI3K/AKT/mTOR pathway and their parallel mechanism in the regulation of ovarian cancer.

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“…We have previously confirmed that a genistein analog can suppress PI3K/AKT signaling5 and the FoxO signaling pathway 6–8. With advances in genomics, network analysis could help dissect multiple human diseases.…”

Section: Introductionmentioning

confidence: 70%

Drug–target–disease network analysis of gene–phenotype connectivity for genistein in ovarian cancer

Zhang¹,

Yang²,

Ni³

et al. 2018

OTT

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PurposeGenistein belongs to the group of isoflavones, which include powerful anticancer agents. Its antitumor properties have been intensively described in many cancers, but related studies assessing ovarian cancer are scarce. The aim of this study was to develop a new method of the underlying mechanisms of genistein’s effects and broaden the perspective of targeted therapies in ovarian carcinoma.Materials and methodsGenistein targets were searched in the DrugBank database. Prediction of drug interactions with targets (including secondary targets) was performed with STRING database. Interaction pairs with overall score above 0.9 were recorded for protein–protein interaction (PPI) network generation based on the Cytoscape software. Genes with intense interconnections were grouped into a module. Then, PPI network modules with significance were assessed using Molecular Complex Detection (MCODE) analysis tool. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed for the critical genes. Furthermore, disease targets were searched in Comparative Toxicogenomics Database (CTD). The overlapping targets were studied using a Kaplan–Meier analysis to evaluate ovarian carcinoma survival.ResultsA total of 13 direct targets and 372 secondary targets were identified for genistein and further analyzed with the MCODE analysis tool to identify critical genes. The top 72 genes were further assessed with KEGG. Then, the term “ovarian cancer” was searched in CTD, and 123 genes associated only with the marker “T” or “M” were recorded. Next, seven overlapping genes (CDKN1B, PTEN, EGFR, MAPK1, MAPK3, PIK3C, and AKT1) resulting from the intersection of three pathways and 123 genes were obtained from CTD. Elevated CDKN1B amounts showed correlation with overall survival (log-rank P=0.021) according to Kaplan–Meier analysis.ConclusionThe current findings indicated that drug–target–disease network analysis represents a useful tool in gene–phenotype connectivity for genistein in ovarian cancer. Our result also showed that CDKN1B is worthy of further research.

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Let-7d increases ovarian cancer cell sensitivity to a genistein analog by targeting c-Myc

Cited by 20 publications

References 34 publications

Let-7d Inhibits Growth and Metastasis in Breast Cancer by Targeting Jab1/Cops5

Let-7d Inhibits Growth and Metastasis in Breast Cancer by Targeting Jab1/Cops5

PIM Kinases and Their Relevance to the PI3K/AKT/mTOR Pathway in the Regulation of Ovarian Cancer

Drug–target–disease network analysis of gene–phenotype connectivity for genistein in ovarian cancer

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Let-7d increases ovarian cancer cell sensitivity to a genistein analog by targeting c-Myc

Cited by 20 publications

References 34 publications

Let-7d Inhibits Growth and Metastasis in Breast Cancer by Targeting Jab1/Cops5

Let-7d Inhibits Growth and Metastasis in Breast Cancer by Targeting Jab1/Cops5

PIM Kinases and Their Relevance to the PI3K/AKT/mTOR Pathway in the Regulation of Ovarian Cancer

Drug&ndash;target&ndash;disease network analysis of gene&ndash;phenotype connectivity for genistein in ovarian cancer

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Drug–target–disease network analysis of gene–phenotype connectivity for genistein in ovarian cancer