Dataset Information

HDAC6, modulated by miR-206, promotes endometrial cancer progression through the PTEN/AKT/mTOR pathway.

ABSTRACT: Endometrial cancer (EC) is the sixth most common cancer in women. Since early EC has a good prognosis, identifying methods for early diagnosis is valuable. Here, we aimed to study the role of HDAC6, which has been indicated important in many kinds of cancers, in EC diagnosis and therapy. First, the expression levels of HDAC6 in EC tissues and cells were measured by qRT-PCR and Western blotting, and through bioinformatics and dual luciferase assays, HDAC6 was found to be a direct target of miR-206. Then, CCK-8, colony formation, wound healing, and Transwell assays were performed; these results indicated that HDAC6 promoted EC cell proliferation, metastasis and invasion, while miR-206 produced the opposite effects. In addition, rescue assays verified that the effect of miR-206 could be reversed by HDAC6, and global gene expression analysis confirmed the relationship between miR-206 and HDAC6. Finally, we measured the levels of PTEN, p-AKT and p-mTOR and other key molecules and speculated that miR-206 might target HDAC6 to suppress EC progression via the PTEN/AKT/mTOR pathway. In conclusion, downregulation of miR-206 and upregulation of HDAC6 in EC may predict poor prognosis, and as the target gene of miR-206, HDAC achieves its carcinogenic effect through the PTEN/AKT/mTOR pathway.

SUBMITTER: Zheng Y

PROVIDER: S-EPMC7046652 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

HDAC6, modulated by miR-206, promotes endometrial cancer progression through the PTEN/AKT/mTOR pathway.

Zheng Yawen Y Yang Xiaohui X Wang Chunyan C Zhang Shuo S Wang Zhiling Z Li Meng M Wang Yuanjian Y Wang Xiaojie X Yang Xingsheng X

Scientific reports 20200227 1

Endometrial cancer (EC) is the sixth most common cancer in women. Since early EC has a good prognosis, identifying methods for early diagnosis is valuable. Here, we aimed to study the role of HDAC6, which has been indicated important in many kinds of cancers, in EC diagnosis and therapy. First, the expression levels of HDAC6 in EC tissues and cells were measured by qRT-PCR and Western blotting, and through bioinformatics and dual luciferase assays, HDAC6 was found to be a direct target of miR-20 ...[more]

PMID: 32107418

Similar Datasets

Project description:Background and Objective: Chemotherapy and radiotherapy are effective treatment options for cervical cancer (CC), but their efficacy is limited by short survival rate of about 5 years particularly for advance stage CC. Bioinformatics analysis combined with experimental in vivo and in vitro data can identify potential markers of tumorigenesis and cancer progression to improve CC prognosis and survival rate of the patients. This study aims to investigate the prognostic value of family with sequence similarity 83, member A (FAM83A) gene and miR-206 in promoting CC progression and the involved genetic signaling pathways. Method: This was a bioinformatic analysis study based on RNA sequencing data of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and verification by in vivo and in vitro experimental data. It was designed to evaluate whether the aberrantly expressed gene signatures could serve as new potential biomarker to improve prognosis prediction in CC. The TCGA RNA sequencing data [306 cervical squamous cell carcinoma (SCC) and endocervical adenocarcinoma samples and 13 adjacent samples] and GEO data (GSE9750 and GSE52903 datasets) were integrated and performed a bioinformatics analysis. Results: The results showed that CC-associated FAM83A gene serves as a key regulator of CC development and progression. Functionally, we observed that FAM83A is significantly overexpressed in CC, which is linked to poor overall survival as well as disease-free survival in CC patients. The in-vitro and in-vivo assessments performed after silencing FAM83A revealed that cell proliferation was significantly inhibited and the S-phase cell cycle arrest was induced. Mechanistically, FAM83A plays a role in PI3K/AKT signaling, and its downstream molecules could promote CC cell proliferation. Furthermore, functionality assessments by in-vitro luciferase reporter system and immunoblot analysis showed that miR-206 was the upstream of FAM83A and negatively correlated with FAM83A. Conclusion: The miR-206/FAM83A/PI3K/AKT signaling pathway possibly serves as a critical effector in CC progression indicating the potential prognostic value of FAM83A gene as a novel biomarker for CC progression.

Project description:BackgroundEndometrial carcinoma (EC) is one of the most common gynecological malignancies among women. Maternal embryonic leucine Zipper Kinase (MELK) is upregulated in a variety of human tumors, where it contributes to malignant phenotype and correlates with a poor prognosis. However, the biological function of MELK in EC progression remains largely unknown.MethodsWe explored the MELK expression in EC using TCGA and GEO databases and verified it using clinical samples by IHC methods. CCK-8 assay, colony formation assay, cell cycle assay, wound healing assay and subcutaneous xenograft mouse model were generated to estimate the functions of MELK and its inhibitor OTSSP167. qRT-PCR, western blotting, co-immunoprecipitation, chromatin immunoprecipitation and luciferase reporter assay were performed to uncover the underlying mechanism concerning MELK during the progression of EC.FindingsMELK was significantly elevated in patients with EC, and high expression of MELK was associated with serous EC, high histological grade, advanced clinical stage and reduced overall survival and disease-free survival. MELK knockdown decreased the ability of cell proliferation and migration in vitro and subcutaneous tumorigenesis in vivo. In addition, high expression of MELK could be regulated by transcription factor E2F1. Moreover, we found that MELK had a direct interaction with MLST8 and then activated mTORC1 and mTORC2 signaling pathway for EC progression. Furthermore, OTSSP167, an effective inhibitor, could inhibit cell proliferation driven by MELK in vivo and vitro assays.InterpretationWe have explored the crucial role of the E2F1/MELK/mTORC1/2 axis in the progression of EC, which could be served as potential therapeutic targets for treatment of EC.FundingThis research was supported by National Natural Science Foundation of China (No:81672565), the Natural Science Foundation of Shanghai (Grant NO:17ZR1421400 to Dr. Zhihong Ai) and the fundamental research funds for central universities (No: 22120180595).

Dataset Information

HDAC6, modulated by miR-206, promotes endometrial cancer progression through the PTEN/AKT/mTOR pathway.

Publications

HDAC6, modulated by miR-206, promotes endometrial cancer progression through the PTEN/AKT/mTOR pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets