Disrupting the Pairing Between
            <i>let-7</i>
            and
            <i>Hmga2</i>
            Enhances Oncogenic Transformation

Mayr, Christine; Hemann, Michael T.; Bartel, David P.

doi:10.1126/science.1137999

Cited by 1,070 publications

(933 citation statements)

References 26 publications

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“…In support of the significance of our findings, reduced expression of let-7 is correlated with poor prognosis, as lung cancer patients with the least let-7 expression had shorter time of survival after surgery (Takamizawa et al, 2004;Yanaihara et al, 2006). We and others subsequently showed that let-7 directly regulates multiple oncogenes, including RAS, MYC and HMGA2 (Johnson et al, 2005;Lee and Dutta, 2007;Mayr et al, 2007;Sampson et al, 2007), and promoters of cell-cycle progression, such as CDC25A, CDK6 and Cyclin D2 (Johnson et al, 2007). Moreover, administration of let-7 blocks the growth of cultured lung cancer cells (Johnson et al, 2007).…”

Section: Introductionsupporting

confidence: 82%

MicroRNAs as potential cancer therapeutics

2008

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Section: Introductionsupporting

confidence: 82%

MicroRNAs as potential cancer therapeutics

2008

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“…This downregulation is due at least in part to impairment of the microprocessor function (Thomson et al, 2006). Among these downregulated micro-RNAs, several have been shown to be bona fide tumor suppressors (Calin et al, 2002;Mayr et al, 2007;Welch et al, 2007;Bonci et al, 2008;Cole et al, 2008;Esquela-Kerscher et al, 2008;Chen et al, 2009;Trang et al, 2010). On the other hand, certain micro-RNAs are overexpressed in cancer.…”

Section: Introductionmentioning

confidence: 99%

Identification of microprocessor-dependent cancer cells allows screening for growth-sustaining micro-RNAs

2011

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“…This could be due to the fact that HMGA2 can be regulated by many microRNAs, such as the wellcharacterized ones in the let-7 family. 26,27 Nevertheless, we found HMGA2 overexpression is significantly associated with high-grade serous ovarian carcinoma 16 in this study (Table 4).…”

Section: Discussionmentioning

confidence: 45%

Expression analysis of MIR182 and its associated target genes in advanced ovarian carcinoma

et al. 2012

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BRCA1/BRCA2 mutations are common and the hallmarks of high-grade serous ovarian carcinoma. We found that MIR182, a negative BRCA1 regulator, is significantly overexpressed in high-grade serous ovarian carcinoma. To examine whether overexpression of MIR182 and its target genes, including BRCA1, HMGA2 (high-mobility group A2), FOXO3 and MTSS1, are associated with high-grade serous ovarian carcinoma tumor types and clinical outcome, we studied MIR182 by in situ hybridization and its target gene expression by immunohistochemistry in 117 cases of advanced ovarian cancer. We found that high-grade serous ovarian carcinoma had significantly higher MIR182 (P ¼ 0.0003) and HMGA2 (P ¼ 0.04) expression, and significantly lower BRCA1 (Po0.0001) and FOXO3 (Po0.001) expression than normal controls. MIR182 is significantly correlated with MTSS1 expression (r ¼ 0.31; Po0.001), whereas other target genes did not show a significant correlation with MIR182, indicating a complicated regulatory mechanisms of these genes in high-grade serous ovarian carcinoma. Among the examined MIR182 target genes, only HMGA2 was significantly associated with serous type carcinomas (Po0.01), ascites (Po0.01) and high death rate (P ¼ 0.02). FOXO3 expression was associated with lower-stage disease (P ¼ 0.04) and solid growth pattern (P ¼ 0.03). MIR182 expression is significantly higher in high-grade serous ovarian carcinoma than in fallopian tubes. Modern Pathology (2012) 25, 1644-1653; doi:10.1038/modpathol.2012.118; published online 13 July 2012Keywords: miR-182; ovarian cancer; BRCA1; HMGA2; MTSS1 High-grade serous ovarian carcinoma is an aggressive and deadly form of ovarian cancer, yet its pathogenesis is poorly understood. Despite significant efforts of clinical researchers, the survival rate of women with high-grade serous ovarian carcinoma has not changed in the past 50 years. 1 These tumors are often high-grade and aggressive at presentation, with a poor prognosis. Recent recognition of the existence of high-grade serous ovarian carcinoma precursor lesions, serous tubal intraepithelial carcinoma, 2,3 in the distal (fimbriated) ends of the fallopian tubes has renewed hope that we will be able to identify early tumorigenic events leading to high-grade serous ovarian carcinoma and reveal new opportunities for early detection and treatment that may decrease the mortality rate among women with this cancer.BRCA1 and BRCA2 mutations are a hallmark of high-grade serous ovarian carcinoma tumorigenesis. 4 Women with germline BRCA1/2 mutations have a 30-70% chance of developing high-grade serous ovarian carcinoma by age 70. 5 Germline BRCA mutations, 6 somatic mutations and epigenetic inactivation of BRCA1/2 (via methylation) can be found in nearly 30% of high-grade serous ovarian carcinoma cases. 7 BRCA1 has a broader role upstream of BRCA2, participating in various cellular

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Disrupting the Pairing Between let-7 and Hmga2 Enhances Oncogenic Transformation

Cited by 1,070 publications

References 26 publications

MicroRNAs as potential cancer therapeutics

MicroRNAs as potential cancer therapeutics

Identification of microprocessor-dependent cancer cells allows screening for growth-sustaining micro-RNAs

Expression analysis of MIR182 and its associated target genes in advanced ovarian carcinoma

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