The Downregulation of MicroRNA-10b and its Role in Cervical Cancer

Zou, Dongling; Zhou, Qi; Wang, Dong; Guan, Li-li; Li, Yuan; Li, Shaolin

doi:10.3727/096504016x14611963142173

Cited by 30 publications

(22 citation statements)

References 27 publications

(6 reference statements)

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“…However, miR-10b may play diverse roles in different tumors. Accumulating evidence showed that miR-10b is increased in breast cancers (43), but only reduced expression of miR-10b was found in cervical cancer (44). The expression level of miR-10b in colorectal cancer is paradoxical as reported by different groups (45,46).…”

Section: Discussionmentioning

confidence: 96%

MicroRNA-10b mediates TGF-β1-regulated glioblastoma proliferation, migration and epithelial-mesenchymal transition

Feng

Xia

et al. 2017

International Journal of Oncology

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Although it is well known that exaggerated proliferation, metastasis and the mesenchymal subtype is related with worst prognoses in glioblastoma (GBM) and that transforming growth factor-β1 (TGF-β1) is a potent factor in regulating the proliferation, migration and epithelial-mesenchymal transition (EMT) phenotype of GBM, the detailed mechanisms are still far from elucidated. MicroRNAs (miRNAs) are small non-coding RNAs which play critical roles in various diseases by regulating target gene expression. We report that miR-10b, a molecule downstream of TGF-β1, is involved in TGF-β1-regulated GBM cell proliferation, migration and EMT. We found that exposure of GBM cells to TGF-β1 significantly upregulated miR-10b expression. Overexpression of miR-10b promotes GBM cell proliferation, migration and EMT, whereas depletion of miR-10b obtained reverse effects. Further studies uncovered that some tumor-associated genes including epithelial cadherin (E-cadherin), apoptotic protease activating factor 1 (Apaf-1) and phosphatase and tensin homolog (PTEN) are target genes of miR-10b. In human GBM xenografts, antagomiR directed against miR-10b markedly suppressed tumor growth, and the tumor volume shrunk from 1252.5±285 to 873.4±205 mm3 after antagomiR‑10b treatment for 3 weeks compared with the control group (P<0.01). Taken together, our data collectively demonstrate that the proliferation, migration and EMT features of GBM cells can be regulated by TGF-β1 stimulation through controlling miR-10b. Thus, our findings provide a rationale for targeting TGF-β1 or miR-10b for the treatment of GBM.

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Section: Discussionmentioning

confidence: 96%

MicroRNA-10b mediates TGF-β1-regulated glioblastoma proliferation, migration and epithelial-mesenchymal transition

Feng

Xia

et al. 2017

International Journal of Oncology

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“…The complex process from normal tissue to cervical cancer involves going through mild dysplasia, moderate dysplasia, severe dysplasia, carcinoma in situ, and infiltrating carcinoma (6). This complex progression involves the abnormal expression of numerous oncogenes and tumor suppressor genes (7). The current primary treatment for cervical cancer is surgery, radiotherapy and chemotherapy (8).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of microRNA‑425‑5p suppresses cervical cancer tumorigenesis by targeting AIFM1

Zhang¹,

Yang²,

Liu³

et al. 2019

Exp Ther Med

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Although microRNA-425-5p (miR-425-5p) has been previously revealed to be upregulated in cervical cancer, the cellular function of miR-425-5p in cervical cancer remains unknown. The aim of the current study was to investigate the cellular function of miR-425-5p and its underlying mechanism in cervical cancer. Reverse transcription-quantitative polymerase chain reaction was used to measure miR-425-5p expression in several cervical cancer cell lines. TargetScan bioinformatics analysis was used to predict apoptosis-inducing factor mitochondria-associated 1 (AIFM1) as a novel target of miR-425-5p, and this was verified by dual-luciferase reporter assay. Furthermore, cell transfections were used to investigate the role of miR-425-5p in cervical cancer. The effect of miR-425-5p on cell viability and apoptosis in HeLa cells was detected by MTT assay and flow cytometry, respectively. The present study demonstrated that miR-425-5p was significantly upregulated in cervical cancer cell lines. In addition, AIFM1 was identified as a direct target of miR-425-5p and negatively regulated by miR-425-5p. Downregulation of miR-425-5p inhibited HeLa cell viability and induced cell apoptosis. Furthermore, downregulation of miR-425-5p significantly increased the protein and mRNA expression levels of cytochrome c, caspase-3, caspase-9 and DNA damage regulated autophagy modulator 1. The effects of miR-425-5p inhibition on HeLa cell viability and apoptosis were significantly reversed by AIFM1 knockdown. In conclusion, the present study demonstrated that miR-425-5p was upregulated in cervical cancer, and downregulation of miR-425-5p inhibited cervical cancer cell growth by targeting AIFM1.

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“…Although several studies suggest that miR-10b acts as either oncogene or tumor suppressor in tumorigenesis, how it contributes to CC remain largely unclear. Zou et al [16] reported that miR-10b was significantly downregulated during cervical cancer progression, but the mechanism of downregulation has not been clarified. In this study, the results also demonstrated that miR-10b was significantly downregulated in CC tissues compared with the controls.…”

Section: Tiam1 Is a Direct And Functional Target Of Mir-10b In CCmentioning

confidence: 99%

“…Our previous study [15] presented some genes including HOXD10, KLF4, HOXA1, TIAM1, MMP9 and etc. Zou et al [16] reported that miR-10b inhibited the cell proliferation and invasion through targeting HOXA1. In this study, dual-luciferase reporter assays identified Tiam1 as a critical downstream target of miR-10b.…”

Section: Cellular Physiology and Biochemistry Cellular Physiology Andmentioning

confidence: 99%

miR-10b Downregulated by DNA Methylation Acts as a Tumor Suppressor in HPV-Positive Cervical Cancer via Targeting Tiam1

Pan

et al. 2018

Cell Physiol Biochem

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Background/Aims: microRNAs (miRNAs) are known to act as oncogenes or tumor suppressors in diverse cancers. Although miR-10b is an oncogene implicated in many tumors, its role in cervical cancer (CC) remains largely unclear. Here, we investigated the function and underlying mechanisms of miR-10b in human CC. Methods: Quantitative RT-PCR was used to measure miR-10b expression in CC and normal tissues, and its association with clinicopathologic features was analyzed. Methylation of CpG sites in the miR-10b promoter was analyzed by methylation sequencing. Cell proliferation, apoptosis, migration, and invasion assays were used to elucidate the biological effects of miR-10b and expression of the target gene was assayed with Western blot. Results: miR-10b was downregulated in CC tissues compared with normal tissues, and less miR-10b expression was associated with larger tumors, vascular invasion and HPV-type 16 positivity. miR-10b expression decreased in HeLa (HPV18-positive) and SiHa (HPV16-positive) cells compared with C-33A (HPV-negative), but increased after treatment with 5-Aza-CdR. Methylation ratio of site -797 in the miR-10b promoter in C-33A was lower than that in HeLa and SiHa. Further analysis indicates that site -797 is located within a transcription factor AP-2A (TFAP2A) binding element. Functionally, overexpression of miR-10b in HeLa and SiHa suppressed cell proliferation, migration and invasion, and induced apoptosis and miR-10b downregulation had opposite effects. Mechanistically, T-cell lymphoma invasion and metastasis 1 (Tiam1) was identified as a direct and functional target of miR-10b. Conclusion: miR-10b acts as a tumor suppressor in CC by suppressing oncogenic Tiam1, and its expression may be downregulated through methylation of TFAP2A binding element by HPV.

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The Downregulation of MicroRNA-10b and its Role in Cervical Cancer

Cited by 30 publications

References 27 publications

MicroRNA-10b mediates TGF-β1-regulated glioblastoma proliferation, migration and epithelial-mesenchymal transition

MicroRNA-10b mediates TGF-β1-regulated glioblastoma proliferation, migration and epithelial-mesenchymal transition

Downregulation of microRNA‑425‑5p suppresses cervical cancer tumorigenesis by targeting AIFM1

miR-10b Downregulated by DNA Methylation Acts as a Tumor Suppressor in HPV-Positive Cervical Cancer via Targeting Tiam1

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