miR-10b Downregulated by DNA Methylation Acts as a Tumor Suppressor in HPV-Positive Cervical Cancer via Targeting Tiam1
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 h...
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Cell Physiol Biochem Press GmbH & Co KG
2018-11-01
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doaj-5dfdaabc38c54e3dad1c82170fcf28b92020-11-25T01:33:15ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-11-015141763177710.1159/000495680495680miR-10b Downregulated by DNA Methylation Acts as a Tumor Suppressor in HPV-Positive Cervical Cancer via Targeting Tiam1Miaomei YuYun XuLili PanYuehua FengKaiming LuoQinfeng MuGuanghua LuoBackground/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.https://www.karger.com/Article/FullText/495680miR-10bMethylationHPVCervical cancerTiam1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Miaomei Yu Yun Xu Lili Pan Yuehua Feng Kaiming Luo Qinfeng Mu Guanghua Luo |
spellingShingle |
Miaomei Yu Yun Xu Lili Pan Yuehua Feng Kaiming Luo Qinfeng Mu Guanghua Luo miR-10b Downregulated by DNA Methylation Acts as a Tumor Suppressor in HPV-Positive Cervical Cancer via Targeting Tiam1 Cellular Physiology and Biochemistry miR-10b Methylation HPV Cervical cancer Tiam1 |
author_facet |
Miaomei Yu Yun Xu Lili Pan Yuehua Feng Kaiming Luo Qinfeng Mu Guanghua Luo |
author_sort |
Miaomei Yu |
title |
miR-10b Downregulated by DNA Methylation Acts as a Tumor Suppressor in HPV-Positive Cervical Cancer via Targeting Tiam1 |
title_short |
miR-10b Downregulated by DNA Methylation Acts as a Tumor Suppressor in HPV-Positive Cervical Cancer via Targeting Tiam1 |
title_full |
miR-10b Downregulated by DNA Methylation Acts as a Tumor Suppressor in HPV-Positive Cervical Cancer via Targeting Tiam1 |
title_fullStr |
miR-10b Downregulated by DNA Methylation Acts as a Tumor Suppressor in HPV-Positive Cervical Cancer via Targeting Tiam1 |
title_full_unstemmed |
miR-10b Downregulated by DNA Methylation Acts as a Tumor Suppressor in HPV-Positive Cervical Cancer via Targeting Tiam1 |
title_sort |
mir-10b downregulated by dna methylation acts as a tumor suppressor in hpv-positive cervical cancer via targeting tiam1 |
publisher |
Cell Physiol Biochem Press GmbH & Co KG |
series |
Cellular Physiology and Biochemistry |
issn |
1015-8987 1421-9778 |
publishDate |
2018-11-01 |
description |
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. |
topic |
miR-10b Methylation HPV Cervical cancer Tiam1 |
url |
https://www.karger.com/Article/FullText/495680 |
work_keys_str_mv |
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