The microRNA-302-367 cluster suppresses the proliferation of cervical carcinoma cells through the novel target AKT1

Cai, Na; Wang, Yidong; Zheng, Pan

doi:10.1261/rna.035295.112

Cited by 91 publications

(88 citation statements)

References 41 publications

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“…The study indicated that ectopic expression of the miR-302-3p-367 cluster inhibited cervical cancer cell proliferation and tumor formation by inducing a cell cycle arrest at the G 1 stage (20). It was further demonstrated that the miR-302-3p-367 cluster suppressed the expression of cyclin D1 and AKT1, while promoted the expression of p27 (Kip1) and p21 (Cip1), which contributed to the inhibition of cervical cancer cell proliferation (20). These findings suggest that miR-302-3p serves a suppressive role in the growth of cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, forced expression of miR-302-3p suppresses tumorigenic gene expression patterns in glioblastoma cells and abolishes transformation-related phenotypes (18). A study by Cai et al (20) reported that the miR-302-367 cluster suppresses the proliferation of cervical carcinoma cells through the novel target AKT1. However, the regulatory mechanism of miR-302-3p underlying cervical cancer metastasis remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA‑302 inhibits cell migration and invasion in cervical cancer by targeting DCUN1D1

Jiang

Hou

et al. 2018

Exp Ther Med

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Abstract. MicroRNA serve crucial roles in a variety of human cancer types. The miR-302-367 cluster has been reported to suppress the proliferation of cervical carcinoma cells through the novel target AKT1; however, the molecular mechanism of miR-302 in cervical cancer metastasis remains unclear. The present study aimed to investigate the clinical significance of miR-302-3p expression in cervical cancer, and to examine the regulatory mechanism of miR-302-3p in the malignant phenotypes of cervical cancer cells. The present data indicated that miR-302-3p was significantly downregulated in cervical cancer tissues compared with the level in adjacent non-tumor tissues, and low expression of miR-302-3p was significantly associated with node metastasis, advanced clinical stage, and poor prognosis in patients with cervical cancer. Restoration of miR-302-3p expression caused a significant reduction in cervical cancer cell migration and invasion. Defective in cullin neddylation 1 domain containing 1 (DCUN1D1) was identified as a novel target gene of miR-302-3p, and miR-302-3p negatively regulated the mRNA and protein expression of DCUN1D1 in cervical cancer HeLa cells. Additionally, overexpression of DCUN1D1 rescued the effects of miR-302-3p on the migration and invasion of cervical cancer cells. Furthermore, DCUN1D1 was upregulated in cervical cancer tissues compared with the levels in adjacent tissues, and its high expression was associated with node metastasis, advanced clinical stage, and shorter survival time in patients with cervical cancer. Notably, a negative correlation between miR-302-3p and DCUN1D1 expression in cervical cancer tissues was observed. Taken together, the present study suggests that miR-302-3p serves a suppressive role in cervical cancer metastasis, partly at least, via directly targeting DCUN1D1. Therefore, miR-302-3p/DCUN1D1 may be a potential therapeutic target for cervical cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MicroRNA‑302 inhibits cell migration and invasion in cervical cancer by targeting DCUN1D1

Jiang

Hou

et al. 2018

Exp Ther Med

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“…We therefore devised a heterologous assay system that relies on the evolutionary conservation of Hnrnpa1 and core proteins involved in the miRNA biogenesis pathway (Akindahunsi et al 2005;Batista et al 2014;Ha and Kim 2014). Because human HeLa cells lack expression of the human mir-430 ortholog, MIR302, which is also restricted to early development (Rosa et al 2009;Cai et al 2013), introduction of zebrafish pri-mir-430 transcripts in HeLa cells could provide a test for the contribution of Hnrnpa1 to the nuclear processing of zebrafish pri-mir-430. Therefore, a construct containing three consecutive miR-430 hairpins derived from the zebrafish miR-430 polycistron was transfected into HeLa cells (Fig.…”

Section: Hnrnpa1 Binds Pri-mir-430 and Regulates Its Processing In Thmentioning

confidence: 99%

Dynamic RNA–protein interactions underlie the zebrafish maternal-to-zygotic transition

Despic

Dejung

et al. 2017

Genome Res.

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During the maternal-to-zygotic transition (MZT), transcriptionally silent embryos rely on post-transcriptional regulation of maternal mRNAs until zygotic genome activation (ZGA). RNA-binding proteins (RBPs) are important regulators of posttranscriptional RNA processing events, yet their identities and functions during developmental transitions in vertebrates remain largely unexplored. Using mRNA interactome capture, we identified 227 RBPs in zebrafish embryos before and during ZGA, hereby named the zebrafish MZT mRNA-bound proteome. This protein constellation consists of many conserved RBPs, some of which are potential stage-specific mRNA interactors that likely reflect the dynamics of RNA-protein interactions during MZT. The enrichment of numerous splicing factors like hnRNP proteins before ZGA was surprising, because maternal mRNAs were found to be fully spliced. To address potentially unique roles of these RBPs in embryogenesis, we focused on Hnrnpa1. iCLIP and subsequent mRNA reporter assays revealed a function for Hnrnpa1 in the regulation of poly(A) tail length and translation of maternal mRNAs through sequence-specific association with 3 ′ UTRs before ZGA. Comparison of iCLIP data from two developmental stages revealed that Hnrnpa1 dissociates from maternal mRNAs at ZGA and instead regulates the nuclear processing of pri-mir-430 transcripts, which we validated experimentally. The shift from cytoplasmic to nuclear RNA targets was accompanied by a dramatic translocation of Hnrnpa1 and other pre-mRNA splicing factors to the nucleus in a transcription-dependent manner. Thus, our study identifies global changes in RNAprotein interactions during vertebrate MZT and shows that Hnrnpa1 RNA-binding activities are spatially and temporally coordinated to regulate RNA metabolism during early development.

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“…The miR-302-367 cluster represses tumorigenesis in cervical carcinoma by targeting Akt1. 45 In addition, the miR-133b family indirectly upregulates the Akt1 pathway during tumorigenesis. 46 The miR-9500 also suppresses metastatic activity compared with the NC or ASO-miR-9500 (Figure 8).…”

Section: Discussionmentioning

confidence: 99%

The novel miR-9500 regulates the proliferation and migration of human lung cancer cells by targeting Akt1

Jung

Lee

et al. 2014

Cell Death Differ

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MicroRNAs have crucial roles in lung cancer cell development. They regulate cell growth, proliferation and migration by mediating the expression of tumor suppressor genes and oncogenes. We identified and characterized the novel miR-9500 in human lung cancer cells. The miR-9500 forms a stem-loop structure and is conserved in other mammals. The expression levels of miR-9500 were reduced in lung cancer cells and lung cancer tissues compared with normal tissues, as verified by TaqMan miRNA assays. It was confirmed that the putative target gene, Akt1, was directly suppressed by miR-9500, as demonstrated by a luciferase reporter assay. The miR-9500 significantly repressed the protein expression levels of Akt1, as demonstrated via western blot, but did not affect the corresponding mRNA levels. Akt1 has an important role in lung carcinogenesis, and depletion of Akt1 has been shown to have antiproliferative and anti-migratory effects in previous studies. In the current study, the overexpression of miR-9500 inhibited cell proliferation and the expression of cell cycle-related proteins. Likewise, the overexpression of miR-9500 impeded cell migration in human lung cancer cells. In an in vivo assay, miR-9500 significantly suppressed Fluc expression compared with NC and ASO-miR-9500, suggesting that cell proliferation was inhibited in nude mice. Likewise, miR-9500 repressed tumorigenesis and metastasis by targeting Akt1. These data indicate that miR-9500 might be applicable for lung cancer therapy.

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The microRNA-302-367 cluster suppresses the proliferation of cervical carcinoma cells through the novel target AKT1

Cited by 91 publications

References 41 publications

MicroRNA‑302 inhibits cell migration and invasion in cervical cancer by targeting DCUN1D1

MicroRNA‑302 inhibits cell migration and invasion in cervical cancer by targeting DCUN1D1

Dynamic RNA–protein interactions underlie the zebrafish maternal-to-zygotic transition

The novel miR-9500 regulates the proliferation and migration of human lung cancer cells by targeting Akt1

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