MicroRNA-200b Suppresses Arsenic-transformed Cell Migration by Targeting Protein Kinase Cα and Wnt5b-Protein Kinase Cα Positive Feedback Loop and Inhibiting Rac1 Activation

Wang, Zhishan; Humphries, Brock A.; Xiao, Hua; Jiang, Yiguo; Yang, Chengfeng

doi:10.1074/jbc.m114.554246

Cited by 57 publications

(31 citation statements)

References 49 publications

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“…In the highly migratory arsenic-transformed cells and basal mesenchymal-like triple negative breast cancer cells, we found that PKCα expression levels are significantly higher, and re-expression of miR-200b reduced PKCα levels and inhibited cell migration as well as mammary tumor metastasis [42, 66]. Subsequent luciferase reporter assays revealed that miR-200b directly targets the 3′UTR of PKCα.…”

Section: The Mir-200 Family In Cancer Metastasismentioning

confidence: 99%

The microRNA-200 family: small molecules with novel roles in cancer development, progression and therapy

2015

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MicroRNAs (miRNAs) are a large family of small non-coding RNAs that negatively regulate protein-coding gene expression post-transcriptionally via base pairing between the 5′ seed region of a miRNA and the 3′ untranslated region (3′UTR) of a messenger RNA (mRNA). Recent evidence has supported the critical role that miRNAs play in many diseases including cancer. The miR-200 family consisting of 5 members (miR-200a, -200b, -200c, -141, -429) is an emerging miRNA family that has been shown to play crucial roles in cancer initiation and metastasis, and potentially be important for the diagnosis and treatment of cancer. While miR-200s were found to be critically involved in the metastatic colonization to the lungs in mouse mammary xenograft tumor models, a large number of studies demonstrated their strong suppressive effects on cell transformation, cancer cell proliferation, migration, invasion, tumor growth and metastasis. This review aims to discuss research findings about the role of the miR-200 family in cancer initiation, each step of cancer metastatic cascade, cancer diagnosis and treatment. A comprehensive summary of currently validated miR-200 targets is also presented. It is concluded that miR-200 family may serve as novel targets for the therapy of multiple types of cancer.

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Section: The Mir-200 Family In Cancer Metastasismentioning

confidence: 99%

The microRNA-200 family: small molecules with novel roles in cancer development, progression and therapy

2015

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“…Taken together, these results indicate that miR-200b down-regulation plays a causal role in arsenite-induced cell malignant transformation and tumorigenesis. In addition, our further follow-up studies also demonstrated that down-regulation of miR-200b plays critical roles in promoting arsenic-transformed cell migration, invasion and tumor angiogenesis (Wang et al, 2012b, 2013, 2014b). Moreover, significant down-regulation of miR-200c level in arsenic-transformed human bronchial epithelial (HBE) cells was recently also observed by other group (Xu et al, 2015a).…”

Section: The Role Of Mirnas In Metal Carcinogen-induced Cell Maligmentioning

confidence: 58%

The role of microRNAs in metal carcinogen-induced cell malignant transformation and tumorigenesis

Humphries

Wang

Yang

2016

Food and Chemical Toxicology

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MicroRNAs (miRNAs), an important component of epigenetic mechanisms of carcinogenesis, have been shown to play crucial roles in cancer initiation, metastasis, prognosis and responses to drug treatment and may serve as biomarkers for early diagnosis of cancer and tools for cancer therapy. Metal carcinogens, such as arsenic, cadmium, hexavalent chromium and nickel, are well-established human carcinogens causing various cancers upon long term exposure. However, the mechanism of metal carcinogenesis has not been well understood, which limits our capability to effectively diagnose and treat human cancers resulting from chronic metal carcinogen exposure. Over recent years, the role of miRNAs in metal carcinogenesis has been actively explored and a growing body of evidence indicates the critical involvement of miRNAs in metal carcinogenesis. This review aims to discuss recent studies showing that miRNAs play important roles in metal carcinogen-induced cell malignant transformation and tumorigenesis. Some thoughts for future further studies in this field are also presented.

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“…The miRTar algorithm identified 372 miRNAs predicted to target the PRKCA 3 ′ UTR, including three of our temperature-responsive miRNAs. PRKCA targeting by hsa-miR-200b (Wang et al 2014), hsa-miR-216b (Deng et al 2013), hsa-miR-203 (Wang et al 2013), and hsa-miR-24-2 * (Martin et al 2014) have been confirmed experimentally. PKCα levels have been shown to increase with increasing levels of hsa-miR-328 in A549 cells (Arora et al 2011).…”

Section: Figure 5 Functional Analysis Of the Pkcαmentioning

confidence: 60%

Shifts in temperature within the physiologic range modify strand-specific expression of select human microRNAs

Potla

Singh

Atamas

et al. 2015

RNA

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Previous studies have revealed that clinically relevant changes in temperature modify clinically relevant gene expression profiles through transcriptional regulation. Temperature dependence of post-transcriptional regulation, specifically, through expression of miRNAs has been less studied. We comprehensively analyzed the effect of 24 h exposure to 32°C or 39.5°C on miRNA expression profile in primary cultured human small airway epithelial cells (hSAECs) and its impact on expression of a targeted protein, protein kinase C α (PKCα). Using microarray, and solution hybridization-based nCounter assays, with confirmation by quantitative RT-PCR, we found significant temperature-dependent changes in expression level of only five mature human miRNAs, representing only 1% of detected miRNAs. Four of these five miRNAs are the less abundant passenger (star) strands. They exhibited a similar pattern of increased expression at 32°C and reduced expression at 39.5°C relative to 37°C. As PKCα mRNA has multiple potential binding sites for three of these miRNAs, we analyzed PKCα protein expression in HEK 293T cells and hSAECs. PKCα protein levels were lowest at 32°C and highest at 39.5°C and specific miRNA inhibitors reduced these effects. Finally, we analyzed cell-cycle progression in hSAECs and found 32°C cells exhibited the greatest G1 to S transition, a process known to be inhibited by PKCα, and the effect was mitigated by specific miRNA inhibitors. These results demonstrate that exposure to clinically relevant hypothermia or hyperthermia modifies expression of a narrow subset of miRNAs and impacts expression of at least one signaling protein involved in multiple important cellular processes.

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MicroRNA-200b Suppresses Arsenic-transformed Cell Migration by Targeting Protein Kinase Cα and Wnt5b-Protein Kinase Cα Positive Feedback Loop and Inhibiting Rac1 Activation

Abstract: Background: MiR-200b is able to inhibit tumor cell migration and metastasis, the underlying mechanism is not well understood.

Cited by 57 publications

References 49 publications

The microRNA-200 family: small molecules with novel roles in cancer development, progression and therapy

The microRNA-200 family: small molecules with novel roles in cancer development, progression and therapy

The role of microRNAs in metal carcinogen-induced cell malignant transformation and tumorigenesis

Shifts in temperature within the physiologic range modify strand-specific expression of select human microRNAs

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