Identification and characterization of lin-28 homolog B (LIN28B) in human hepatocellular carcinoma

Guo, Yingqiu; Chen, Yongxin; Ito, Hirotaka; Watanabe, Akira; Ge, Xijin; Kodama, Tatsuhiko; Aburatani, Hiroyuki

doi:10.1016/j.gene.2006.07.011

Cited by 267 publications

(295 citation statements)

References 38 publications

Supporting

Mentioning

270

Contrasting

Unclassified

Order By: Relevance

“…As recently reported by Viswanathan et al (2008), miRNA processing by Lin28 plays an important role in cancer progression. These data are consistent with the promotion of tumor cell growth by Lin28B as reported by Guo et al (2006). In addition, studies by Yu et al (2007) indicate that Lin28 plays a critical role in enabling stem cell pluripotency.…”

supporting

confidence: 89%

Src Regulates the Expression of Lin28: Implications for Cell Growth, Adhesion, and Communication

Khusial¹,

Vadla

Goldberg³

2009

Cell Communication & Adhesion

View full text Add to dashboard Cite

supporting

confidence: 89%

Src Regulates the Expression of Lin28: Implications for Cell Growth, Adhesion, and Communication

Khusial¹,

Vadla

Goldberg³

2009

Cell Communication & Adhesion

View full text Add to dashboard Cite

“…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

View full text Add to dashboard Cite

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.

show abstract

“…Western blot analysis of SK-N-AS cells transfected with miR-34a showed a significant reduction in E2F3 protein in cells Figure 4 (a) Validation of miR-34a mRNA targets. Luciferase constructs were made by ligating oligonucleotides containing the putative target site into the XbaI site of the pGL3-control vector (promega) as described previously (Guo et al, 2006) (see Supplementary methods). A significant reduction in luciferase activity is detected when an oligonucleotide containing the exact complementary sequence of miR-34a is cloned into the construct (pGL3_miR-34a).…”

mentioning

confidence: 99%

MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells

2007

View full text Add to dashboard Cite

Neuroblastoma (NB) is one of the most common forms of cancer in children, accounting for 15% of pediatric cancer deaths. The clinical course of these tumors is highly variable and is dependent on such factors as age at presentation, stage, ploidy and genomic abnormalities. Hemizygous deletion of chromosome 1p occurs in approximately 30% of advanced stage tumors, is associated with a poor prognosis, and likely leads to the loss of one or more tumor suppressor genes. We show here that microRNA (miRNA)-34a (1p36.23) is generally expressed at lower levels in unfavorable primary NB tumors and cell lines relative to normal adrenal tissue and that reintroduction of this miRNA into three different NB cell lines causes a dramatic reduction in cell proliferation through the induction of a caspase-dependent apoptotic pathway. As a potential mechanistic explanation for this observation, we demonstrate that miR-34a directly targets the messenger ribonucleic acid (mRNA) encoding E2F3 and significantly reduces the levels of E2F3 protein, a potent transcriptional inducer of cell-cycle progression. Furthermore, miR-34a expression increases during retinoic acidinduced differentiation of the SK-N-BE cell line, whereas E2F3 protein levels decrease. Thus, adding to the increasing role of miRNAs in cancer, miR-34a may act as a suppressor of NB tumorgenesis.

show abstract

Identification and characterization of lin-28 homolog B (LIN28B) in human hepatocellular carcinoma

Cited by 267 publications

References 38 publications

Src Regulates the Expression of Lin28: Implications for Cell Growth, Adhesion, and Communication

Src Regulates the Expression of Lin28: Implications for Cell Growth, Adhesion, and Communication

Identification of small molecule inhibitors of Zcchc11 TUTase activity

MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells

Contact Info

Product

Resources

About