Pluripotent factor lin-28 and its homologue lin-28b in epithelial ovarian cancer and their associations with disease outcomes and expression of let-7a and IGF-II

Lu, Lingeng; Katsaros, Dionyssios; Shaverdashvili, Khvaramze; Qian, Biyun; Wu, Yibo; Longrais, Irene A. Rigault de la; Preti, Mario; Menato, Guido; Yu, Herbert

doi:10.1016/j.ejca.2009.05.003

Cited by 91 publications

(75 citation statements)

References 35 publications

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“…The authors also detected Lin28 expression in normal ovarian surface epithelium; this cell type is thought to contribute, at least in part, to the origin of EOC. In contrast, Lu et al (2009) have found no significant correlation between Lin28 expression levels and tumor grade, disease stage or overall survival. The possibility exists that these discrepancies result from RNA-based analyses that do not faithfully reflect expression at the protein level.…”

Section: Introductionmentioning

confidence: 83%

Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer

2010

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Section: Introductionmentioning

confidence: 83%

Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer

2010

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“…Lin28A/B expression is associated with advanced disease in hepatocellular carcinoma (HCC), chronic myeloid leukemia (CML), Wilms' tumor, ovarian carcinoma, and germ cell tumors. 16,22,[35][36][37][38][39][40][41][42][43][44] Moreover, Lin28A/Lin28B expression is associated with poor clinical outcome and patient survival in HCC, ovarian cancer, Neuroblastoma, and Medulloblastoma. 16,18,35,45 Therefore, identification of small molecule drugs that specifically inhibit the Lin28/ let-7 pathway might prove to be a powerful approach for cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

Identification of small molecule inhibitors of Zcchc11 TUTase activity

Lin

Gregory

2015

RNA Biology

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The RNA-binding protein Lin28 regulates the expression of the let-7 family of microRNAs (miRNAs) during early embryonic development. Lin28 recruits the 3 0 terminal uridylyl transferase (TUTase) Zcchc11 (TUT4) and/or Zcchc6 (TUT7) to precursor let-7 RNA (pre-let-7) to selectively block let-7 biogenesis. Uridylated pre-let-7 is targeted for decay by the downstream exonuclease Dis3l2 thereby preventing processing to mature let-7. Activation of this oncogenic pathway via up-regulation of Lin28 expression promotes cellular transformation, drives tumorigenesis in mouse models, and is frequently observed in a wide variety of cancer. Recent proof-of-principle experiments showed that Zcchc11 knockdown inhibits the tumorigenicity of Lin28-expressing human cancer cells and established this enzyme as a possible new therapeutic target for human malignancies. However, there are currently no known pharmacological agents capable of targeting this novel enzyme. In this study we developed and applied a sensitive biochemical assay that monitors Zcchc11 activity. Using this assay we performed an automated high-throughput screen of »15,000 chemicals to identify putative TUTase inhibitors. Several of these small molecules were validated as specific inhibitors of Zcchc11 activity. Our results demonstrate the feasibility of screening for TUTase inhibitors and present a relatively simple platform that can be exploited for future drug discovery efforts aimed at restoring let-7 expression in cancer.

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“…It has been reported that both expression of LIN28A and LIN28B are reac- (4,(42)(43)(44)(45)(46)(47). However, the expression and distribution of LIN28A in different types of epithelial tumors is still unknown.…”

Section: Reactivation Of Strong Lin28a Expression In 10% Of Humanmentioning

confidence: 99%

“…In human tumors, LIN28A/LIN28B expression is up-regulated/reactivated (4,(42)(43)(44)(45)(46)(47)(48)(49)(50)(51) and may function as an oncogene promoting malignant transformation (42,43,52,53), inducing metastasis (43,46,(52)(53)(54), regulating inflammation (5,43), and maintaining the cancer stem cells (43,45,(55)(56)(57). Clinical studies have indicated that higher levels of LIN28A/LIN28B expression are associated with poor clinical outcomes (44,58,59) and that LIN28 family polymorphisms may influence susceptibility to ovarian (60) and breast (61) cancers.…”

mentioning

confidence: 99%

Lin-28 Homologue A (LIN28A) Promotes Cell Cycle Progression via Regulation of Cyclin-dependent Kinase 2 (CDK2), Cyclin D1 (CCND1), and Cell Division Cycle 25 Homolog A (CDC25A) Expression in Cancer

Zhong

Lin

et al. 2012

Journal of Biological Chemistry

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Background: LIN28A may function as a critical oncogene in human cancer. Results: LIN28A controls expression of numerous cell cycle regulatory genes, including CDK2, CCND1, and CDC25A, in cancer. Conclusion: LIN28A promotes cell cycle progression in cancer mediated by both let-7-dependent and -independent mechanisms. Significance: Our data shed new light on how LIN28A regulates cell cycle in cancer.

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Pluripotent factor lin-28 and its homologue lin-28b in epithelial ovarian cancer and their associations with disease outcomes and expression of let-7a and IGF-II

Cited by 91 publications

References 35 publications

Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer

Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer

Identification of small molecule inhibitors of Zcchc11 TUTase activity

Lin-28 Homologue A (LIN28A) Promotes Cell Cycle Progression via Regulation of Cyclin-dependent Kinase 2 (CDK2), Cyclin D1 (CCND1), and Cell Division Cycle 25 Homolog A (CDC25A) Expression in Cancer

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