MicroRNA-30a suppresses breast tumor growth and metastasis by targeting metadherin

Zhang, Ning; Wang, X; Huo, Qiang; Sun, Mingxia; Cheng, Can; Liu, Z; Hu, Guohong; Yang, Qifeng

doi:10.1038/onc.2013.286

Cited by 132 publications

(120 citation statements)

References 52 publications

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“…These bioinformatics strategies might not predict all of the potential targets of microRNAs. What is more, only miRanda and microRNA.org were applied in the study of Baransikin et al In contrast, the prediction results showed that IRS2 was a potential target of miR-30a in the study of Zhang et al (24). Interestingly, miR-30b/miR-30c (miR-30b/c) has a different function from miR-30a even though they share the same seed sequences.…”

Section: Discussionmentioning

confidence: 71%

Role of MicroRNA 30a Targeting Insulin Receptor Substrate 2 in Colorectal Tumorigenesis

Zhang

Tang

Qin

et al. 2015

Molecular and Cellular Biology

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d MicroRNAs (miRNAs) are dysregulated in many types of malignant diseases, including colorectal cancer. miRNA 30a (miR-30a) is a member of the miR-30 family and has been implicated in many types of cancers. In this study, we determined the expression of miR-30a in human colon cancer tissues and cell lines. miR-30a was found to be significantly downregulated in both the tissues and cell lines. Furthermore, overexpression of miR-30a inhibited, while silencing of miR-30a promoted, cell proliferation, migration, and invasion in vitro. Consistently, stable overexpression of miR-30a suppressed the growth of colon cancer cell xenografts in vivo. Moreover, bioinformatic algorithms and luciferase reporter assays revealed that insulin receptor substrate 2 (IRS2) is a direct target of miR-30a. Further functional studies suggested that repression of IRS2 by miR-30a partially mediated the tumor suppressor effect of miR-30a. In addition, miR-30a inhibited constitutive phosphorylation of Akt by targeting IRS2. Additionally, clinicopathological analysis indicated that miR-30a has an inverse correlation with the staging in patients with colon cancer. Taken together, our study provides the first evidence that miR-30a suppressed colon cancer cell growth through inhibition of IRS2. Thus, miR-30a might serve as a promising therapeutic strategy for colon cancer treatment. Colorectal cancer (CRC) is the third most common cancer in males and females, with an estimated 142,820 new cases and 50,830 deaths in the United States in 2013. The overall CRC incidence is 5% in the general population, and the 5-year survival rate ranges from 40% to 60% (1). Despite the improvement of currently available treatment strategies, including surgical resection, radiotherapy, and chemotherapy, the survival rate of patients with CRC has changed little over the past 10 years. Almost 50% of CRC patients will die of the disease, mainly due to metastasis to the liver. Thus, it is imperative to achieve earlier diagnosis and better tailoring of treatments to improve CRC outcomes.MicroRNAs (miRNAs) are a family of endogenous small noncoding RNAs that regulate gene expression via the sequence-specific base pairing on the 3= untranslated regions (3= UTRs) of target mRNAs, resulting in mRNA cleavage or translation inhibition (2). More than 30% of the protein-coding genes are controlled by miRNAs, as indicated by bioinformatics predictions. miRNAs are involved in a plethora of biological processes, such as proliferation, migration, invasion, and apoptosis (3, 4). In recent years, miRNAs have been recognized as critical regulators in development and progression of cancer, including CRC (5-8).miRNA 30a (miR-30a) is a member of the miR-30 family, which consists of six distinct mature miRNA sequences: miR-30a/ miR-30c-2, miR-30d/miR-30b, and miR-30e/miR-30c-1 (9). There is considerable evidence suggesting that the dysregulation of miR-30a is correlated with several types of malignant tumors, including breast cancer, lung cancer, thyroid cancer, gastric cancer, and leuke...

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Section: Discussionmentioning

confidence: 71%

Role of MicroRNA 30a Targeting Insulin Receptor Substrate 2 in Colorectal Tumorigenesis

Zhang

Tang

Qin

et al. 2015

Molecular and Cellular Biology

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“…6B) as well as cell growth inhibition was clearly visible in RPE-1 cells overexpressing miR-30a, suggesting that ectopic expression of this miRNA was functional and related to the observed tumor suppression. Consequently, miR-30a has been described as a suppressor of tumor growth and inhibitor of cell migration and invasion (Baraniskin et al 2012;Cheng et al 2012;Kumarswamy et al 2012;Zhang et al 2013). Altogether, our results indicate that miR-30b/c and not other miR-30 family members are specifically involved in anoikis resistance.…”

Section: Discussionsupporting

confidence: 66%

Novel small RNA expression libraries uncover hsa-miR-30b and hsa-miR-30c as important factors in anoikis resistance

Moreno-Mateos

Barragán

Torres

et al. 2013

RNA

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MicroRNAs (miRNAs) have been widely studied in order to elucidate their biological functions. MicroRNA microarrays or miRNA overexpression libraries generated by synthesis and cloning of individual miRNAs have been used to study their different roles. In this work, we have developed a novel methodology to express mature miRNAs and other small RNAs from a double convergent RNA polymerase III promoter. We show that the generated miRNAs function similarly to those processed from primary transcripts or pri-miRNAs. This system allowed us to produce a lentiviral library expressing the whole population of small RNAs present in a metastatic cell line. A functional screening using this library led to the identification of hsa-miR-30b and hsa-miR-30c as negative regulators of cell death induced by loss of attachment (anoikis). Importantly, we demonstrated that the acquisition of anoikis resistance via these miRNAs is achieved through down-regulation of caspase 3 expression. Moreover, overexpression of these miRNAs resulted in a decrease of other types of caspase 3-dependent cell death and enhanced the survival of MCF10A acinar cells in morphogenesis assays, suggesting a putative role as oncomirs. In summary, this novel methodology provides a powerful and effective way for identifying novel small RNAs involved in a particular biological process.

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“…miR30 family members are among one of the most dysregulated miRNAs in metastatic cancers, each with a potential role in cancer metastasis (21). Although miR30a expression has been reported to be downregulated in metastatic breast cancer and colorectal cancer, its tumor suppressor function is not well understood (22,23). Specifically, downregulation of miR30a in ATC has been previously reported but overexpression of this miRNA did not affect cell proliferation in two ATC cell lines (FRO, FB-1; ref.…”

Section: Discussionmentioning

confidence: 99%

miR30a Inhibits LOX Expression and Anaplastic Thyroid Cancer Progression

et al. 2015

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Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies, but its genetic drivers remain little understood. In this study, we report losses in expression of the miRNA miR30a, which is downregulated in ATC compared with differentiated thyroid cancer and normal tissue. miR30a downregulation was associated with advanced differentiated thyroid cancer and higher mortality. Mechanistically, we found miR30a decreased cellular invasion and migration, epithelialmesenchymal transition marker levels, lysyl oxidase (LOX) expression, and metastatic capacity. LOX was identified as a direct target of miR30a that was overexpressed in ATC and associated with advanced differentiated thyroid cancer and higher mortality rate. Consistent with its role in other cancers, we found that LOX inhibited cell proliferation, cellular invasion, and migration and metastasis in vitro and in vivo. Together, our findings establish a critical functional role for miR30a downregulation in mediating LOX upregulation and thyroid cancer progression, with implications for LOX targeting as a rational therapeutic strategy in ATC. Cancer Res; 75(2); 367-77.Ó2014 AACR.

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MicroRNA-30a suppresses breast tumor growth and metastasis by targeting metadherin

Cited by 132 publications

References 52 publications

Role of MicroRNA 30a Targeting Insulin Receptor Substrate 2 in Colorectal Tumorigenesis

Role of MicroRNA 30a Targeting Insulin Receptor Substrate 2 in Colorectal Tumorigenesis

Novel small RNA expression libraries uncover hsa-miR-30b and hsa-miR-30c as important factors in anoikis resistance

miR30a Inhibits LOX Expression and Anaplastic Thyroid Cancer Progression

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