miR-30a Suppresses Cell Migration and Invasion Through Downregulation of PIK3CD in Colorectal Carcinoma

Zhong, Ming; Bian, Zhengqian; Wu, Zhi‐Yong

doi:10.1159/000343362

Cited by 91 publications

(74 citation statements)

References 31 publications

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“…Several studies demonstrated that miR-30a could reduce the oncogenic abilities of breast cancer and lung cancer by inhibiting epithelial-to-mesenchymal transition (EMT), invasiveness, and autophagy of cancer, depending on their targets (10,11,21). In particular, two other studies have shown that miR-30a is able to induce growth inhibition and cell migration and invasion suppression in colorectal cancer by targeting DTL and PIK3CD, respectively (22,23). In line with these observations, we found that miR-30a acts as a tumor suppressor by targeting IRS2.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…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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“…Recent studies have revealed that the miR-30 family plays important roles in pronephros development, hepatobiliary duct formation, and myogenesis in zebrafish (Agrawal et al, 2009;Hand et al, 2009); the miR-30 family also regulates cancer metastasis in humans and mice (Zhong et al, 2013;Zhang et al, 2016). However, the roles of the miR-30 family in neuroimmunological diseases have not been reported.…”

Section: Discussionmentioning

confidence: 99%

Disulfiram and Diphenhydramine Hydrochloride Upregulate miR-30a to Suppress IL-17-Associated Autoimmune Inflammation

Zhao

Sun

Guan

et al. 2016

Journal of Neuroscience

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T-helper 17 (Th17) cells play an important role in the pathogenesis of multiple sclerosis (MS), an autoimmune demyelinating disease that affects the CNS. In the present study, MicroRNA sequencing (miRNA-seq) was performed in mouse Th0 and Th17 cells to determine the critical miRNAs that are related to Th17 differentiation. We found that miR-30a was significantly downregulated during mouse Th17 differentiation. In addition, the level of miR-30a in CD4 ϩ T cells from peripheral blood of MS patients and experimental autoimmune encephalomyelitis (EAE) animal models was also decreased and inversely correlated with the expression of interleukin 17a, the canonical cytokine of Th17 cells. Moreover, overexpression of miR-30a inhibited Th17 differentiation and prevented the full development of EAE, whereas interference of miR-30a promoted Th17 differentiation. Mechanism studies showed that miR-30a reduced IRF4 expression by specifically binding with the 3Ј-untranslated region. Through screening of 640 different Food and Drug Administration (FDA)-approved drugs, we found that disulfiram and diphenhydramine hydrochloride were effective candidates for inhibiting Th17 differentiation and ameliorating EAE development through upregulating miR-30a. To our knowledge, the present work is not only the first miRNA-seq study focusing on Th17 differentiation, but also the first chemical screening for FDA-approved drugs that inhibit Th17 differentiation through regulating miRNA expression.

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miR-30a Suppresses Cell Migration and Invasion Through Downregulation of PIK3CD in Colorectal Carcinoma

Cited by 91 publications

References 31 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

miR30a Inhibits LOX Expression and Anaplastic Thyroid Cancer Progression

Disulfiram and Diphenhydramine Hydrochloride Upregulate miR-30a to Suppress IL-17-Associated Autoimmune Inflammation

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