LIN28: A regulator of tumor-suppressing activity of let-7 microRNA in human breast cancer

Sakurai, Minako; Miki, Yasuhiro; Masuda, Mariko; Hata, Shuko; Shibahara, Yukiko; Higuchi, Hisashi; Suzuki, Takashi; Sasano, Hironobu

doi:10.1016/j.jsbmb.2011.10.007

Cited by 57 publications

(48 citation statements)

References 32 publications

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“…The let-7 family is a tumor-suppressor gene family, which is often inactivated in human cancers, including breast cancer. As one of the target genes of the let-7 family, lin-28 homolog A (LIN28) has been reported to promote tumorigenic activity by suppressing let-7 miRNA maturation in breast cancer cells (23). miR-100 has been reported to inhibit tumorigenesis in oral squamous cell carcinoma, ovarian cancer and breast cancer by interfering with proliferation and survival signaling (24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

Predicting associations between microRNAs and target genes in breast cancer by bioinformatics analyses

et al. 2016

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Abstract. Breast cancer is the leading type of cancer among females. However, the association between microRNAs (miRNAs) and target genes in breast tumorigenesis is poorly studied. The original data set GSE26659 was downloaded from the Gene Expression Omnibus, and then the differentially expressed miRNAs among 77 breast cancer patients and 17 controls were identified using the Limma package in R software. Furthermore, breast cancer-related differentially expressed miRNAs were selected from a human miRNA disease database and their target genes were selected from five miRNA databases. Then, functional analysis was performed for the target genes followed by construction of a miRNA-target gene network. A total of 34 differentially expressed miRNAs were identified, including 13 breast cancer-related miRNAs. Moreover, the target genes of the 13 miRNAs were significantly enriched in regulation of transcription (P=7.43E-09) and pathways related to cancer (P=3.33E-11). Finally, eight upregulated miRNAs (including hsa-miR-425) and five downregulated miRNAs (including hsa-miR-143, hsa-miR-145 and hsa-miR-125b) were identified in the miRNA-target gene network. In conclusion, using bioinformatics approaches, we demonstrate that the changes in regulation of transcription and cancer pathways may play significant roles in the process of breast cancerogenesis. Differentially expressed miRNAs and their target genes may be new targets for breast cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Predicting associations between microRNAs and target genes in breast cancer by bioinformatics analyses

et al. 2016

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“…Loss of let-7 family members correlates with poor survival rates in many cancers (26–29), in part by inhibiting the RAS signaling pathway by targeting several elements within the 3′UTRs of KRAS and NRAS (30,33,68). Consistent with the hypothesis that miRNAs function by targeting multiple members of the same pathway, the top hits for let-7c identified by 3′LIFE were enriched for multiple genes within the RAS signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…The let-7 family members are broadly characterized as tumor suppressors; reduction in the expression of multiple family members is observed in many cancers and correlates with poor survival outcomes (26–29). let-7 miRNAs target genes that promote cell proliferation [RAS (30), HMGA2 (26), E2F5 (31,32)] and invasion and metastasis [MMP11, PBX3 (33)].…”

Section: Introductionmentioning

confidence: 99%

3′LIFE: a functional assay to detect miRNA targets in high-throughput

Wolter

Kotagama

Pierre-Bez

et al. 2014

Nucleic Acids Research

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MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene output at the post-transcriptional level by targeting degenerate elements primarily in 3′untranslated regions (3′UTRs) of mRNAs. Individual miRNAs can regulate networks of hundreds of genes, yet for the majority of miRNAs few, if any, targets are known. Misexpression of miRNAs is also a major contributor to cancer progression, thus there is a critical need to validate miRNA targets in high-throughput to understand miRNAs' contribution to tumorigenesis. Here we introduce a novel high-throughput assay to detect miRNA targets in 3′UTRs, called Luminescent Identification of Functional Elements in 3′UTRs (3′LIFE). We demonstrate the feasibility of 3′LIFE using a data set of 275 human 3′UTRs and two cancer-relevant miRNAs, let-7c and miR-10b, and compare our results to alternative methods to detect miRNA targets throughout the genome. We identify a large number of novel gene targets for these miRNAs, with only 32% of hits being bioinformatically predicted and 27% directed by non-canonical interactions. Functional analysis of target genes reveals consistent roles for each miRNA as either a tumor suppressor (let-7c) or oncogenic miRNA (miR-10b), and preferentially target multiple genes within regulatory networks, suggesting 3′LIFE is a rapid and sensitive method to detect miRNA targets in high-throughput.

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“…Meanwhile, they also found relevance between Lin28B expression and Ki67. 24 Moreover, HER2 overexpression is also regarded as an aggressive clinical characteristic in breast cancer. 25 It has been found that Lin28A was overexpressed in HER2-positive breast cancers.…”

Section: Discussionmentioning

confidence: 99%

Lin28B Expression Correlates with Aggressive Clinicopathological Characteristics in Breast Invasive Ductal Carcinoma

Xie

Wang²,

Nie³

et al. 2014

Cancer Biotherapy and Radiopharmaceuticals

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Lin28B is a RNA-binding protein that inhibits the let-7 microRNA family and acts as an oncogene in various human malignant diseases. Conversely, the members of let-7 family function as tumor suppressers and are often inactivated in cancers. The interaction of Lin28B/let-7 plays a crucial part of tumorigenesis. In this study, the authors examined the Lin28B expression using immunohistochemistry in 190 breast cancers and analyzed the correlation of Lin28B immunostaining and clinicopathological characteristics. Breast cancer patients previously diagnosed with invasive ductal carcinomas were enrolled in this study. All cases went through surgical procedures as the initial treatment. The characteristics of every case were collected, including tumor size, pathologic grade, metastatic lymphoid nodes, and estrogen receptor α (ERα), progesterone receptor (PR), and HER2 status. The immunostaining was scored by two independent investigators. Eighty-three (43.7%) of 190 cases showed positive expression of Lin28B. Lin28B immunostaining was increased in tumors compared with the adjacent tissues. Overexpression of Lin28B was linked to poor differentiation, advanced-stage disease, and Ki67-positive status (all p<0.05). Besides, Lin28B expression was significantly different among breast cancer subtypes. This study addresses the role of Lin28B in breast cancers and provides insight of its predictive effects in disease development.

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LIN28: A regulator of tumor-suppressing activity of let-7 microRNA in human breast cancer

Cited by 57 publications

References 32 publications

Predicting associations between microRNAs and target genes in breast cancer by bioinformatics analyses

Predicting associations between microRNAs and target genes in breast cancer by bioinformatics analyses

3′LIFE: a functional assay to detect miRNA targets in high-throughput

Lin28B Expression Correlates with Aggressive Clinicopathological Characteristics in Breast Invasive Ductal Carcinoma

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