MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting DTL

Baraniskin, Alexander; Birkenkamp‐Demtröder, Karin; Maghnouj, Abdelouahid; Zöllner, Hannah; Münding, Johanna; Klein-Scory, Susanne; Reinacher‐Schick, Anke; Schwarte-Waldhoff, Irmgard; Schmiegel, Wolff; Hahn, Stephan A.

doi:10.1093/carcin/bgs020

Cited by 152 publications

(128 citation statements)

References 39 publications

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“…It was reported to be remarkably downregulated in thyroid anaplastic carcinoma compared with normal thyroid tissue, suggesting a tumor suppressive role in thyroid anaplastic carcinomas (18). Similarly, Baraniskin et al (19) reported that miR-30a-5p was able to suppress proliferation and induce apoptosis of colon carcinoma cells by inhibiting the expression of DTL, which was frequently overexpressed in colorectal cancer. On the contrary, miR-30a-5p is overexpressed in glioma tissues and cell lines when compared with normal brain tissues, and its level of expression is positively associated with tumor grade of malignancy (11).…”

Section: Discussionmentioning

confidence: 96%

MicroRNA-30a-5p suppresses proliferation, invasion and tumor growth of hepatocellular cancer cells via targeting FOXA1

et al. 2017

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Abstract. Deregulation of microRNAs (miRs) has been observed in a variety of types of human cancer. Previously, miR-30a-5p has been demonstrated to exhibit a suppressive role in hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unclear. The present study aimed to elucidate the regulatory mechanism of miR-30a-5p in proliferation and invasion of HCC cells. Quantitative reverse transcription polymerase and western blotting were used to examine mRNA and protein expression of Forkhead box A1 (FOXA1). MTT and Transwell assays were performed to examine proliferation and invasion. Luciferase reporter assay was used to determine the association between miR-30a-5p and FOXA1. The data indicated that miR-30a-5p was significantly downregulated in HCC tissues compared with normal liver tissues. Furthermore, the level of miR-30a-5p was lower in HCC tissues with higher histological grade and advanced tumor stage compared with tissues with lower histological grade and tumor stage. Additionally, restoration of miR-30a-5p expression decreased the proliferation and invasion of HCC HepG2 and SMMC-7721 cells. FOXA1, a novel oncogene in HCC, was further identified as a target of miR-30a-5p. Furthermore, high expression of miR-30a-5p suppressed mRNA and protein expression of FOXA1, while overexpression of FOXA1 reversed the suppressive effect of miR-30a-5p on proliferation and invasion of HepG2 and SMMC-7721 cells. FOXA1 was markedly upregulated in HCC tissues compared with normal liver tissues, and its level was higher in HCC tissues with higher histological grade and advanced tumor stage. In addition, it was found that overexpression of miR-30a-5p significantly suppressed the tumor growth of HCC cells in nude mice. Taken together, the present study supports that miR-30a-5p inhibits the proliferation, invasion, and tumor growth of HCC cells, partly at least, by inhibition of FOXA1 expression, and therefore suggests that miR-30a-5p may serve as a potential candidate for HCC therapy.

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Section: Discussionmentioning

confidence: 96%

MicroRNA-30a-5p suppresses proliferation, invasion and tumor growth of hepatocellular cancer cells via targeting FOXA1

et al. 2017

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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: Discussionmentioning

confidence: 58%

“…S6). Using previously described lentiviral systems (Gaziel-Sovran et al 2011;Baraniskin et al 2012), miR-30a and miR-30d were overexpressed in RPE-1 cells (Supplemental Fig. S7), and pro-CASP3 depletion was checked by Western blot (Fig.…”

Section: Design and Validation Of The Processed Mirnas Expression Systemmentioning

confidence: 99%

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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“…Furthermore, miR-140 has been shown to be essential for normal endochondral bone development and proliferation [38], while miR-103 is linked to insulin sensitivity [39] and intestinal cell proliferation [40]. Recently, miR-30a has been found to suppress tumor growth in colon carcinoma by targeting DTL gene [41]. MiR-101b cooperates with let-7 miRNAs in tumors to inhibit cell proliferation [42], and it also participates in the FGF-2-regulated cell proliferation, migration and angiogenesis through an NDY1/KDM2B-miR-101-EZH2 pathway [43].…”

Section: Potential Marker Mirnas May Distinguish Bsc From Pscmentioning

confidence: 99%

MicroRNA profiles and potential regulatory pattern during the early stage of spermatogenesis in mice

Luo

Hao

et al. 2014

Sci. China Life Sci.

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Spermatogenesis is a complicated and poorly understood process that relies on the precise regulation of the self-renewal and differentiation of spermatogonia. In many organisms, microRNAs (miRNAs) are involved in multiple developmental processes as critical regulators of transcriptional and post-transcriptional gene silencing. This study investigated the expression pattern of miRNAs in type B spermatogonia cells (BSc) and primary spermatocytes (PSc) of mice, using a high-throughput small RNA sequencing system. The results revealed that the expression levels of Let-7 family miRNAs were remarkably high in both cell types. Furthermore, the expression levels of miR-21, miR-140-3p, miR-103, miR-30a, miR-101b and miR-99b were decreased during the transformation from BSc to PSc. These miRNAs target vital genes that participate in apoptosis, cell proliferation and differentiation, junction assembly and cell cycle regulation. These results highlight the indispensable role of miRNAs in spermatogenesis. Spermatogenesis is a complex process in which spermatogonial stem cells form spermatozoa following mitotic, meiotic and post-meiotic phases. The process of spermatogenesis is highly sensitive to fluctuations in the environment and involves numerous endocrine and paracrine signals to coordinate the self-renewal of spermatogonial stem cells (SCCs) and spermatogonial differentiation [1]. Spermatogenesis is characterized by the phase-specific expression of many genes that are exclusively expressed in spermatogenic cells.With the development and application of technologies such as gene cloning, gene expression and functional characterization, many spermatogenesis-related genes have been identified in the past few years, some of which were found to play important roles in spermatogenesis [2]. Spermatogenesis-associated genes such as cyclins, proto-oncogenes and genes for azoospermia factor, cytoskeleton, heat shock proteins, nucleoprotein transition, centrin and apoptosis are involved in highly conserved landmark events such as meiotic recombination, formation of the synaptonemal complex, sister chromatid cohesion, spermiogenesis during post-

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MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting DTL

Cited by 152 publications

References 39 publications

MicroRNA-30a-5p suppresses proliferation, invasion and tumor growth of hepatocellular cancer cells via targeting FOXA1

MicroRNA-30a-5p suppresses proliferation, invasion and tumor growth of hepatocellular cancer cells via targeting FOXA1

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

MicroRNA profiles and potential regulatory pattern during the early stage of spermatogenesis in mice

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