MicroRNA-21 targets tumor suppressor genes in invasion and metastasis

Zhu, Shuomin; Wu, Hailong; Wu, Fangting; Nie, Daotai; Shen, Sheng; Mo, Yin Yuan

doi:10.1038/cr.2008.24

Cited by 1,003 publications

(814 citation statements)

References 48 publications

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“…The antiapoptotic role of miR-21, first described in glioblastoma (Chan et al, 2005), has been further characterized in cholangiocarcinoma (Meng et al, 2006) and multiple myeloma cells (Loffler et al, 2007). Moreover, miR-21 is implicated in breast cancer cell growth and invasiveness Zhu et al, 2008), in agreement with its detection in a subset of miRNAs highly correlating with biopathologic features of breast cancer .…”

Section: Introductionmentioning

confidence: 69%

“…They encode for tumor suppressor proteins, including the phosphatase PTEN in human hepatocellular carcinoma (Meng et al, 2007), the cytoskeleton component tropomyosin-1 (TPM1) in breast cancer cells , the translational regulator PDCD4 in colorectal carcinoma and breast cancer cells (Asangani et al, 2008;Frankel et al, 2008;Zhu et al, 2008), maspin in breast cancer cells (Zhu et al, 2008). Moreover, in the recent report on the PMA-mediated induction of miR-21 in PML cells, the transcript encoding the nuclear factor NFI-B was characterized as a novel miR-21 target .…”

Section: Discussionmentioning

confidence: 99%

“…A RAS-dependent AP-1-miR-21-PDCD4 regulatory loop F Talotta et al inverse correlation with miR-21 (Asangani et al, 2008;Zhu et al, 2008). Interestingly, PDCD4 was characterized as a powerful inhibitor of AP-1 activity (Yang et al, 2003b;Wang et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, PDCD4 was characterized as a powerful inhibitor of AP-1 activity (Yang et al, 2003b;Wang et al, 2007). In addition to being translationally repressed by miR-21 (Asangani et al, 2008;Frankel et al, 2008;Zhu et al, 2008), PDCD4 itself is a translational repressor, inhibiting the translation initiation factor eIF4A (Yang et al, 2003a). PDCD4 inhibits the activity of AP-1 and other transcription factors, including b-catenin/Tcf (Wang et al, 2007) and Sp1/Sp3 (Leupold et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

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An autoregulatory loop mediated by miR-21 and PDCD4 controls the AP-1 activity in RAS transformation

et al. 2008

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The transcription factor AP-1 plays key roles in tumorigenesis, by regulating a variety of protein-coding genes, implicated in multiple hallmarks of cancer. Among non-coding genes, no AP-1 target has been described yet in tumorigenesis. MicroRNAs (miRNAs) are negative post-transcriptional regulators of protein-coding genes. miRNA expression signatures are highly relevant in cancer and several tumor-associated miRNAs (oncomirs) play critical roles in oncogenesis. Here, we show that the miRNA miR-21, which represents the most frequently upregulated oncomir in solid tumors, is induced by AP-1 in response to RAS. By analyzing validated miR-21 targets, we have found that the tumor suppressors PTEN and PDCD4 are downregulated by RAS in an AP-1-and miR-21-dependent fashion. We further show that, given the role of PDCD4 as negative regulator of AP-1, the miR-21-mediated downregulation of PDCD4 is essential for the maximal induction of AP-1 activity in response to RAS. Our data reveal a novel mechanism of positive autoregulation of the AP-1 complex in RAS transformation and disclose the function of oncomirs as critical targets and regulators of AP-1 in tumorigenesis.

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Section: Introductionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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An autoregulatory loop mediated by miR-21 and PDCD4 controls the AP-1 activity in RAS transformation

et al. 2008

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“…Previously identified or proposed miR-21 targets include tropomyosin-1 (an inhibitor of anchorageindependent cell proliferation) (Zhu et al, 2008), PTEN (a negative regulator of two MMP genes, MMP2 and MMP9, and of FAK phosphorylation) (Meng et al, 2006), programmed cell death-4 (PDCD4) (Asangani et al, 2008;Frankel et al, 2008) and maspin (two proteins implicated in suppression of invasion and metastasis) (Zhu et al, 2008), and MARCKS (a protein kinase-C-substrate regulating cell motility) (Li et al, 2009). RECK also regulates proteases and suppresses growth, invasion and metastasis of tumor cells (Takahashi et al, 1998;Oh et al, 2001;Morioka et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia and RAS-signaling pathways converge on, and cooperatively downregulate, the RECK tumor-suppressor protein through microRNAs

et al. 2010

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Cancer cells show characteristic gene expression profiles. Recent studies support the potential importance of micro-RNA (miRNA) expression signatures as biomarkers and therapeutic targets. The membrane-anchored protease regulator RECK is downregulated in many cancers, and forced expression of RECK in tumor cells results in decreased malignancy in animal models. RECK is also essential for mammalian development. In this study, we found that RECK is a target of at least three groups of miRNAs (miR-15b/16, miR-21 and miR-372/373); that RECK mutants lacking the target sites for these miRNA show augmented tumor/metastasis-suppressor activities; and that miR-372/373 are upregulated in response to hypoxia through HIF1a and TWIST1, whereas miR-21 is upregulated by RAS/ERK signaling. These data indicate that the hypoxia-and RAS-signaling pathways converge on RECK through miRNAs, cooperatively downregulating this tumor suppressor and thereby promoting malignant cell behavior.

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Control of Receptor Function by MicroRNAs in Breast Cancer

Piovan

Iorio

2013

MicroRNAs in Medicine

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MicroRNA-21 targets tumor suppressor genes in invasion and metastasis

Cited by 1,003 publications

References 48 publications

An autoregulatory loop mediated by miR-21 and PDCD4 controls the AP-1 activity in RAS transformation

An autoregulatory loop mediated by miR-21 and PDCD4 controls the AP-1 activity in RAS transformation

Hypoxia and RAS-signaling pathways converge on, and cooperatively downregulate, the RECK tumor-suppressor protein through microRNAs

Control of Receptor Function by MicroRNAs in Breast Cancer

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