The mechanisms involved in miR-9 regulated apoptosis in cervical cancer by targeting FOXO3

Zhang, Haiyan; Zhang, Zhen; Wang, Surong; Zhang, Shiqian; Bi, Junying

doi:10.1016/j.biopha.2018.03.019

Cited by 22 publications

(10 citation statements)

References 28 publications

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“…Inhibition of miR-9-5p had a smaller effect on cell viability in SiHa than in CaSki (metastasis, HPV16), probably due to the high endogenous levels of miR-9-5p SiHa. Previous studies have reported similar effects of miR-9-5p in SiHa and HeLa [18,22]. While FOXO3 and IL6 were shown to be targeted by miR-9-5p in these studies, we could not confirm downregulation of FOXO3 and IL6 upon miR-9-5p overexpression ( Figure S1).…”

Section: Discussioncontrasting

confidence: 59%

“…Zhang et al, on the other hand, reported that low expression of miR-9-5p in cervical ACs compared to healthy cervical tissue is due to hypermethylation of all three miR-9-5p precursor genes [22]. In line with these observations, miR-9-5p was shown to play an oncogenic function in HPV16-tranformed keratinocytes and HPV16-positive SiHa cells originating from a cervical SCC, while a tumor suppressive role has been described in the HPV18-positive cervical AC cell line HeLa [8,18,22]. Taken together, these studies suggest that miR-9-5p expression in cervical cancer may be cell type and/or hrHPV type-dependent and are suggestive of a dual functional role of miR-9-5p in cervical cancer.…”

Section: Introductionmentioning

confidence: 57%

“…This versatile function of miR-9-5p in human cancers has recently been reviewed by Nowek et al and likely results from a variety of downstream targets in different 2 of 15 cellular contexts [17]. Among others, cyclin D1 (CCND1), E-cadherin (CDH1), FOXO3, IL6, and NOTCH1 have been described as direct targets of miR-9-5p [17,18].…”

Section: Introductionmentioning

confidence: 96%

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miR-9-5p Exerts a Dual Role in Cervical Cancer and Targets Transcription Factor TWIST1

Babion

Jaspers

Splunter

et al. 2019

Cells

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Squamous cell carcinoma (SCC) and adenocarcinoma (AC) represent the major cervical cancer histotypes. Both histotypes are caused by infection with high-risk HPV (hrHPV) and are associated with deregulated microRNA expression. Histotype-dependent expression has been observed for miR-9-5p, showing increased expression in SCC and low expression in AC. Here, we studied the regulation and functionality of miR-9-5p in cervical SCCs and ACs using cervical tissue samples and hrHPV-containing cell lines. Expression and methylation analysis of cervical tissues revealed that low levels of miR-9-5p in ACs are linked to methylation of its precursor genes, particularly miR-9-1. Stratification of tissue samples and hrHPV-containing cell lines suggested that miR-9-5p depends on both histotype and hrHPV type, with higher expression in SCCs and HPV16-positive cells. MiR-9-5p promoted cell viability and anchorage independence in cervical cancer cell lines SiHa (SCC, HPV16) and CaSki (metastasized SCC, HPV16), while it played a tumor suppressive role in HeLa (AC, HPV18). TWIST1, a transcription factor involved in epithelial-to-mesenchymal transition (EMT), was established as a novel miR-9-5p target. Our results show that miR-9-5p plays a dual role in cervical cancer in a histotype- and hrHPV type-dependent manner. MiR-9-5p mediated silencing of TWIST1 suggests two distinct mechanisms towards EMT in cervical cancer.

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Section: Discussioncontrasting

confidence: 59%

Section: Introductionmentioning

confidence: 57%

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miR-9-5p Exerts a Dual Role in Cervical Cancer and Targets Transcription Factor TWIST1

Babion

Jaspers

Splunter

et al. 2019

Cells

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“…Subsequently, we explored the diagnostic efficacy of some specific miRNAs, including miR-9 and miR-205, which had favorable diagnostic efficacy. According to the findings of Zhang et al, inhibition of miR-9 could induce apoptosis of CC cells by combining to FOXO3 gene, providing potential molecular targets for CC patients [67]. Likewise, Aishanjiang et al also found that miR-9 was overexpressed in CC lines and clinical tissues, which can directly target FOXO1 gene to enhance invasion and migration of CC [68].…”

Section: Discussionmentioning

confidence: 99%

Identification of Circulating MicroRNAs as a Promising Diagnostic Biomarker for Cervical Intraepithelial Neoplasia and Early Cancer: A Meta-Analysis

Jiang

Hu²,

Zuo

et al. 2020

BioMed Research International

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Background. Cervical cancer (CC) is one of the most common female malignant tumors. And cervical intraepithelial neoplasia (CIN) is the precancerous lesion of CC, which can progress to invasive CC. MicroRNAs (miRNAs) have been found to be potential diagnostic biomarkers for CIN or CC. However, recently, the lack of sufficient studies about the diagnostic value of miRNAs for CIN made it challenging to separately investigate the diagnostic efficacy of miRNAs for CIN. Likewise, the conclusions among those studies were discordant. Therefore, we conducted this meta-analysis, aimed at evaluating the diagnostic efficacy of miRNAs for CIN and CC patients. Methods. Literature search was performed in PubMed, Embase, and Web of Science databases. Pooled sensitivity, specificity, and other diagnostic parameters were calculated through Stata 14.0 software. Furthermore, subgroup analyses and metaregression analysis were conducted to explore the main sources of heterogeneity. Results. Ten articles covering 50 studies were eligible, which included 5,908 patients and 4,819 healthy individuals. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.81 (95% CI, 0.77-0.85), 0.86 (95% CI, 0.83-0.89), 5.9 (95% CI, 4.5-7.7), 0.22 (95% CI, 0.17-0.28), 27 (95% CI, 17-44), and 0.91 (95% CI, 0.88-0.93), respectively. Additionally, the ethnicity and internal reference were the main sources of heterogeneity. Conclusions. Circulating miRNAs can be a promising noninvasive diagnostic biomarker for CIN and early CC, especially miR-9 and miR-205, which need to be verified by large-scale studies.

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“…For instance, Chen et al found that nuclear accumulation of FoxO3a in tumor cells was linked with the increased radiosensitivity of esophageal carcinoma (15). Meanwhile FoxO3a, which could be regulated by miRNAs, will notably induce radiation resistance in several cancer (28)(29)(30)(31)(32). Based on the early ndings, we postulated that functional inhibition of FoxO3a expression may attenuate the radioresistance of malignant glioma.…”

Section: Discussionmentioning

confidence: 83%

Suppression of FoxO3a Increases Responsiveness of Glioma Cells to Radiation Treatment

Wang

Chen

Liao

et al. 2020

Preprint

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Background Glioblastoma multiforme (GBM) is the most deadly and common cerebral malignant tumors in adults. Radiotherapy is one of the major treatments for GBM patients. Further work is urgently required to discover the mechanisms conferring GBM radioresistance.Methods Reverse transcription-quantitative PCR was applied to detect the relative expression of FoxO3a in glioma cell lines after radiation. Lentivirus mediated FoxO3a knockdown cells were constructed and were confirmed by RT-qPCR and western blot. Plate clone formation assay and flow cytometry was used to determine the colony formation ability and cell apoptosis following radiotherapy, respectively. DNA damage and levels of apoptotic proteins were determined by comet assay and western blot.Results FoxO3a was significantly up-regulated in GBM cells in response to radiation. Knockdown of FoxO3a enhances the responsiveness of glioma cells to radiotherapy, the cell clonogenic formation and DNA repair process with elevated the percentage of apoptotic cells. Moreover, suppression of FoxO3a increased pro-apoptotic proteins Caspase 3, Caspase 7 and Bax levels after radiotherapy.Conclusions The study indicated that suppression of FoxO3a increased radiosensitivity in glioma cells, which might be a potential diagnostic and therapeutic target. Inhibition of FoxO3a expression enhances the responsiveness of glioma cells to radiotherapy, and its proliferation ability is weaker than that of normal Foxo3 cells

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The mechanisms involved in miR-9 regulated apoptosis in cervical cancer by targeting FOXO3

Cited by 22 publications

References 28 publications

miR-9-5p Exerts a Dual Role in Cervical Cancer and Targets Transcription Factor TWIST1

miR-9-5p Exerts a Dual Role in Cervical Cancer and Targets Transcription Factor TWIST1

Identification of Circulating MicroRNAs as a Promising Diagnostic Biomarker for Cervical Intraepithelial Neoplasia and Early Cancer: A Meta-Analysis

Suppression of FoxO3a Increases Responsiveness of Glioma Cells to Radiation Treatment

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