Regulation of Cell Proliferation and Migration by miR-203 via GAS41/miR-10b Axis in Human Glioblastoma Cells

Pal, Dhananjaya; Mukhopadhyay, Debasmita; Ramaiah, M. Janaki; Sarma, P.N.; Bhadra, Utpal; Bhadra, Manika Pal

doi:10.1371/journal.pone.0159092

Cited by 22 publications

(15 citation statements)

References 57 publications

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“…Decreased miR-203a levels may yield an imbalance in proliferation and differentiation that may yield uncontrolled proliferation and tumor formation. This may explain why expression of miR-203a is diminished in bladder cancer, prostate cancer, esophageal squamous cell carcinoma, and human glioblastoma 14 - 17 . We demonstrated in the current study that the expression of miR-203a is significantly lower in cholesteatoma than in normal retroauricular skin (Figure 1 A,B,C).…”

Section: Discussionmentioning

confidence: 99%

“…Investigators previously have demonstrated that miR-203a is specific to epithelial tissue; affects the growth, differentiation, and function of keratinocytes; and is an important contributor to skin development 11 - 13 . In many tumors, miR-203a has been shown to prevent or suppress cancer 14 - 17 . Like the skin, a cholesteatoma is composed primarily of keratinocytes; like a tumor, the keratinocytes of a cholesteatoma exhibit abnormal proliferation and migration.…”

Section: Introductionmentioning

confidence: 99%

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Downregulation of MiR-203a Disinhibits Bmi1 and Promotes Growth and Proliferation of Keratinocytes in Cholesteatoma

Zang¹,

Hui²,

Yang³

et al. 2018

Int. J. Med. Sci.

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Background: Keratinocytes are the predominant cell type in a cholesteatoma, and microRNA (miR)-203a has been shown to be essential for the growth and differentiation of keratinocytes. The regulatory mechanisms of miR-203a and Bmi1—the predicted target of miR-203a that is associated with cholesteatoma—have not been clarified.Methods: Real-time PCR and western blot were carried out for the detection of miRNAs, mRNAs, and proteins, including miR-203a, Bmi1, and phosphorylated (p-)Akt. Immunohistochemical staining was applied to observe the expression and distribution of Bmi1 and of p-Akt in cholesteatoma and in control retroauricular skin. The dual luciferase reporter assay was used to analyze the relationship between miR-203a and Bmi1. Ectopic miR-203a and Bmi1 were transfected into an immortalized line of human keratinocytes (HaCaT cells), and the roles of these molecules in cell proliferation, apoptosis, and migration were explored.Results: Cholesteatoma tissues were characterized by downregulation of miR-203a and concomitant upregulation of Bmi1. Results of the dual-luciferase reporter assay indicated that Bmi1 was a direct target gene of miR-203a. Silencing of miR-203a increased Bmi1 expression; promoted proliferation, colony formation, and migration of HaCaT cells; and inhibited apoptosis. Moreover, p-Akt was significantly increased in cholesteatoma tissues and was positively correlated with Bmi1. Suppression of Bmi1 reduced p-Akt expression in HaCaT cells; subsequent inhibition of miR-203a reversed this phenomenon.Conclusions: Our results reveal that miR-203a may regulate cholesteatoma growth and proliferation by targeting Bmi1. These findings provide insight for the development of novel nonsurgical options for cholesteatoma.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Downregulation of MiR-203a Disinhibits Bmi1 and Promotes Growth and Proliferation of Keratinocytes in Cholesteatoma

Zang¹,

Hui²,

Yang³

et al. 2018

Int. J. Med. Sci.

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“…Oligonucleotide has-miR-203 mimics (miR-203) were designed as described previously [19], and a non-specific sequence was used as a negative control (miR-NC). The miR-203 plasmid construct was chemically synthesized by Gene Pharma (Shanghai, China) and is shown in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Bufalin Inhibits Cellular Proliferation and Cancer Stem Cell-Like Phenotypes via Upregulation of MiR-203 in Glioma

Liu

Weng

et al. 2017

Cell Physiol Biochem

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Background/Aims: Prior studies have shown that bufalin inhibits cellular proliferation and induces apoptosis in various human cancers. MicroRNA-203 (miR-203) has been shown to function as an important regulator of tumor progression at various stages. In this study, we investigated the effect of miR-203 expression and bufalin treatment on glioma cell proliferation and stem cell-like phenotypes. Methods: We used cell viability assay, colony formation assay, cell apoptosis assay and neurosphere formation assay to dectect the treatment effect of bufalin on U251 and U87 cells. Cells were transfected with the miR-203 mimic without bufalin treatment or cells were transfected with anti-miR-203 under bufalin treatment, the above expreiments were repeated. RT-PCR was employed to quantify miR-203 expression. Western blot was performed to detect the stem cell-like (CSC) markers, OCT4 and SOX2. Luciferase activity assay was used to determine whether the SPARC is the target of miR-203. Results: Bufalin treatment inhibited cell proliferation, colony formation, and CSC phenotypes and increased cell apoptosis and expression of miR-203. Furthermore, overexpression of miR-203 led to similar outcomes as bufalin treatment with respect to the cell viability, colony formation, cell apoptosis and the phenotypes of glioma cells. While anti-miR-203 attenuated the inhibitory effects of bufalin as promoting cell proliferation, colony formation and CSC phenotyes and inhibiting cell apoptosis. In addition, we identified SPARC as a novel target gene of miR-203. Conclusions: These findings suggest that miR-203 plays an important role in bufalin’s ability to inhibit the growth of glioma cells and the development of stem cell-like phenotypes.

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“…Its mechanism of action to regulate tumor cell invasion and metastasis has become a focus in the research field. 18,19 And a large number of studies confirmed that tumor invasion and metastasis are related to miRNA. 20,21 Yanaihara et al 22,23 found that miR-125a was located in 19q13.41 and analyzed the lung cancer tissues and the corresponding adjacent lung tissues with core chip, which displayed that expression of miR-125a in lung cancer tissues was lower than that in the adjacent lung tissues.…”

mentioning

confidence: 99%

MicroRNA-125a-5p plays a role as a tumor suppressor in lung carcinoma cells by directly targeting STAT3

et al. 2017

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Increasing evidence supports that the dysregulation of microRNA expression plays an important role in the process of tumor occurrence and development. Studies have found that mir-125a-5p expression was downregulated in a variety of tumors, but the effects and mechanism of mir-125a-5p in lung cancer are still unclear. The aim of this study is to detect the expression of mir-125a-5p in lung cancer tissues and lung cancer cell lines and to explore the effects of mir-125a-5p on the biological characteristics of lung cancer cells; thus, this study aims to provide new methods and new strategies for the treatment of lung cancer. The result from quantitative reverse transcription polymerase chain reaction showed that the expression of miR-125a-5p was significantly lower in lung cancer tissues and lung cancer cell lines (95-D, A549, HCC827, and NCI-H1299) than that in normal tissue adjacent to lung cancer or normal human bronchial epithelial cells. In order to explore the function and mechanism of mir-125a-5p in lung cancer cells, miR-125a-5p mimic or mir-125a-5p inhibitor was transfected into A549 cells. Mir-125a-5p displayed an obvious upregulation in A549 cells transfected with miR-125a-5p and an obvious downregulation in A549 cells transfected with mir-125a-5p inhibitor compared to that in A549 cells transfected with control miRNA. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, BrdU staining, flow cytometry, and Transwell assay showed that the upregulation of miR-125a-5p could significantly decrease the cell viability, proliferation, and invasion of lung cancer cells and increase apoptosis of lung cancer cells. The downregulation of miR-125a-5p provided very contrasting results. Computational algorithms predicted that the STAT3 is a target of miR-125a-5p. Here, we validated that miR-125a-5p could directly bind to the 3'-untranslated region of STAT3, and miR-125a-5p overexpression could significantly inhibit the protein expression of STAT3. These results suggested that mir-125a-5p can regulate the expression of STAT3 in lung cancer cells. To further verify whether mir-125a-5p can play a biological role through regulating STAT3, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, flow cytometry, and Transwell analysis demonstrated that overexpression of STAT3 can reverse the cells' biological effects induced by mir-125a-5p overexpression. Mir-125a-5p downregulated in lung cancer tissue and cell lines can negatively regulate STAT3 protein expression. Taken together, mir-125a-5p inhibited the proliferation and invasion of lung cancer cells and facilitated lung cancer cell apoptosis through suppressing STAT3. Enhancing the expression of miR-125a-5p is expected to benefit the therapy for the patients with lung cancer.

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Regulation of Cell Proliferation and Migration by miR-203 via GAS41/miR-10b Axis in Human Glioblastoma Cells

Cited by 22 publications

References 57 publications

Downregulation of MiR-203a Disinhibits Bmi1 and Promotes Growth and Proliferation of Keratinocytes in Cholesteatoma

Downregulation of MiR-203a Disinhibits Bmi1 and Promotes Growth and Proliferation of Keratinocytes in Cholesteatoma

Bufalin Inhibits Cellular Proliferation and Cancer Stem Cell-Like Phenotypes via Upregulation of MiR-203 in Glioma

MicroRNA-125a-5p plays a role as a tumor suppressor in lung carcinoma cells by directly targeting STAT3

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