Differential Regulation of <i>LET-7</i> by LIN28B Isoform–Specific Functions

Mizuno, Rei; Chatterji, Priya; Andres, Sarah F.; Hamilton, Kathryn E.; Simon, L; Foley, Shawn W.; Jeganathan, Arjun; Madison, Blair B.; Rustgi, Anil K.

doi:10.1158/1541-7786.mcr-17-0514

Cited by 13 publications

(15 citation statements)

References 56 publications

(93 reference statements)

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“…Finally, to validate up-regulation of Wnt targets identified via RNA-seq, we used siRNA to knock down IMP1 in Caco2 cells ( Supplementary Fig. 4A,B) that endogenously express LIN28B (Mizuno et al 2018). We observed significant up-regulation of multiple WNT targets with IMP1 knockdown, corroborating our findings in a second, independent cell line (Supplemental Fig.…”

Section: Imp1 Loss Is a Significant Regulator Of Translation In The Csupporting

confidence: 80%

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The LIN28B–IMP1 post-transcriptional regulon has opposing effects on oncogenic signaling in the intestine

et al. 2018

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RNA-binding proteins (RBPs) are expressed broadly during both development and malignant transformation, yet their mechanistic roles in epithelial homeostasis or as drivers of tumor initiation and progression are incompletely understood. Here we describe a novel interplay between RBPs LIN28B and IMP1 in intestinal epithelial cells. Ribosome profiling and RNA sequencing identified as a principle node for gene expression regulation downstream from In vitro and in vivo data demonstrate that epithelial IMP1 loss increases expression of WNT target genes and enhances LIN28B-mediated intestinal tumorigenesis, which was reversed when we overexpressed IMP1 independently in vivo. Furthermore, IMP1 loss in wild-type or LIN28B-overexpressing mice enhances the regenerative response to irradiation. Together, our data provide new evidence for the opposing effects of the LIN28B-IMP1 axis on post-transcriptional regulation of canonical WNT signaling, with implications in intestinal homeostasis, regeneration and tumorigenesis.

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Section: Imp1 Loss Is a Significant Regulator Of Translation In The Csupporting

confidence: 80%

“…down IMP1 in Caco2 cells (Supplemental Fig. 4A,B), which endogenously express LIN28B (Mizuno et al 2018). We observed significant up-regulation of multiple WNT targets with IMP1 knockdown in these cells.…”

Section: Imp1 Plays a Functional Role In Reserve Intestinal Stem Cellsmentioning

confidence: 56%

The LIN28B–IMP1 post-transcriptional regulon has opposing effects on oncogenic signaling in the intestine

et al. 2018

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“…However, LIN28B-short isoform lacks the inhibitory ability against the processing by microprocessors. Namely, LIN28B-short isoform functions as a competitor against the LIN28B-long isoform in the context of let-7 maturation [ 25 ].…”

Section: Biogenesis Of Let-7 Micrornas ( mentioning

confidence: 99%

“…Although only a single paper reported that the high let-7g expression was significantly associated with the chemoresistance against S-1 in CRC patients [ 77 ], most of the studies have shown that the downregulation of let-7 contributes to the chemoresistance in the context of CRC. One of the underlying mechanisms by which the downregulated let-7 contributes to the chemoresistance is that the decreased let-7 induces the expression of DNA excision repair protein, excision repair cross-complementing group 1 (ERCC1), which contributes to the resistance against cisplatin or 5-FU [ 25 ].…”

Section: Functions Of Let-7 In the Colonic Tumomentioning

confidence: 99%

The Molecular Basis and Therapeutic Potential ofLet-7MicroRNAs against Colorectal Cancer

Mizuno

Kawada

Sakai

2018

Canadian Journal of Gastroenterology and Hepatology

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Although a number of studies have revealed the underlying mechanisms which regulate the development of colorectal cancer (CRC), we have not completely overcome this disease yet. Accumulating evidence has shown that the posttranscriptional regulation by the noncoding RNAs such as microRNAs plays an important role in the development or progression of CRC. Among a number of microRNAs, the let-7 microRNA family that was first discovered in C. elegans and conserved from worms to humans has been linked with the development of many types of cancers including CRC. The expression level of let-7 microRNAs is temporally low during the normal developmental processes, while elevated in the differentiated tissues. The let-7 microRNAs regulate the cell proliferation, cell cycle, apoptosis, metabolism, and stemness. In CRC, expressions of let-7 microRNAs have been reported to be reduced, and so let-7 microRNAs are considered to be a tumor suppressor. In this review, we discuss the mechanisms regulating the let-7 microRNA expression and the downstream targets of let-7 in the context of intestinal tumorigenesis. The application of let-7 mimics is also highlighted as a novel therapeutic agent.

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“…This is a random commercial molecule which has been extensively tested in human cell lines by us and others. In addition, it has been widely demonstrated that this control does not alter known functions of miRNAs and mRNAs (54)(55)(56)(57). In this study, the results suggested that this scrambled sequence did not affect the expression of miR-34a or that of EMT-related genes evaluated at 24 and 48 h post-transfection in the MCF-10F and MDA-MB-231 cell lines.…”

Section: Discussionmentioning

confidence: 59%

Curcumin rescues breast cells from epithelial‑mesenchymal transition and invasion induced by anti‑miR‑34a

et al. 2019

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Breast cancer is the most prevalent type of cancer among women worldwide and it is characterized by a high morbidity. Curcumin is a naturally occurring compound derived from the rhizome of Curcuma longa and is known to have antioxidant and anticarcinogenic properties. Emerging evidence has indicated that microRNAs (miRNAs or miRs) function as oncogenes or tumor suppressor genes to control invasion and migration. The aim of this study was to evaluate the effects of curcumin on genes implicated in epithelial-mesenchymal transition (EMT) and to examine the involvement of Rho-A in the migration and invasion of MCF-10F and MDA-MB-231 breast cell lines. Furthermore, to the best of our knowledge, this is the first study to examine the effects of curcumin on Rho-A and on genes involved in EMT, such as Axl, Slug and CD24 in order to determine whether the compound is able to prevent migration and invasion by targeting miRNAs as a regulator of such genes. Specifically, we focused on miR-34a which acts as a tumor suppressor gene in human breast cell lines. The present study demonstrated that the Axl, Slug and CD24 genes were implicated in EMT, and Rho-A was also involved in the migration and invasion of MCF-10F and MDA-MB-231 cell lines. Curcumin also acted upon the miRNA as a regulator of genes implicated in EMT and upon Rho-A as well, affecting the migration and invasion of the cells. This occurred independently of their estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) receptors in the non-malignant MCF-10F and malignant MDA-MB-231 breast cell lines, which are both negative for such receptors.

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Differential Regulation of LET-7 by LIN28B Isoform–Specific Functions

Cited by 13 publications

References 56 publications

The LIN28B–IMP1 post-transcriptional regulon has opposing effects on oncogenic signaling in the intestine

The LIN28B–IMP1 post-transcriptional regulon has opposing effects on oncogenic signaling in the intestine

The Molecular Basis and Therapeutic Potential ofLet-7MicroRNAs against Colorectal Cancer

Curcumin rescues breast cells from epithelial‑mesenchymal transition and invasion induced by anti‑miR‑34a

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