MiR-376a and Histone Deacetylation 9 Form A Regulatory Circuitry in Hepatocellular Carcinoma

Zheng, Yan; Chen, Huan; Yin, Miao; Ye, Xiaoqian; Chen, Guiqian; Zhou, Xinmei; Li, Yin; Zhang, Chengwen; Ding, Baoyue

doi:10.1159/000369733

Cited by 34 publications

(25 citation statements)

References 29 publications

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“…Because of the poor overall survival associated with it, new therapies are urgently needed. MicroRNAs have been found to play a dual role in the progression of tumors, including HCC: some act as oncogenes, and some as tumor suppressor genes [19-21]. For example, miR-155 is upregulated in HCC, promotes cancer cell invasion, and is a predictor of poor survival of hepatocellular carcinoma [22].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-873 Promotes Cell Proliferation, Migration, and Invasion by Directly Targeting TSLC1 in Hepatocellular Carcinoma

Han¹,

Zhang²,

Ni³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has the third highest mortality rate among all cancers. MicroRNAs are a class of endogenous, single-stranded short noncoding RNAs. The purpose of this study was to study the role of microRNA-873 in HCC. Methods: The expression of miRNA-873 and tumor suppressor in lung cancer 1 (TSLC1) in HCC tissues and cell lines was detected by real-time quantitative RT-PCR (RT-qPCR) or western blot. A CCK-8 assay was used to examine cell proliferation; flow cytometry was used to assess the cell cycle; the Transwell migration assay was used to test for metastasis. Luciferase assays were performed to assess whether TSLC1 was a novel target of miRNA-873. Results: We showed that miRNA-873 was upregulated in HCC tissues and cell lines compared with the normal control. Knockdown of miRNA-873 inhibited the growth and metastasis of HepG2 and accelerated G1 phase arrest, while overexpression of miRNA-873 had the opposite effect. The dual-luciferase reporter assays revealed that TSLC1 was a novel target of miRNA-873. Further study showed that TSLC1 was decreased in HCC tissues and cell lines. There was a negative correlation between the expression levels of TSLC1 and miRNA-873. The effect of miRNA-873 overexpression was neutralized by TSLC1. We also found that miRNA-873 activated the PI3K/AKT/mTOR signaling pathway and promoted HCC. Conclusions: Our data demonstrated that miRNA-873 promoted HCC progression by targeting TSLC1 and provided a new target for the therapy of HCC.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-873 Promotes Cell Proliferation, Migration, and Invasion by Directly Targeting TSLC1 in Hepatocellular Carcinoma

Han¹,

Zhang²,

Ni³

et al. 2018

Cell Physiol Biochem

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“…Interestingly, miR-127-3p and miR-376a-3p are located in miRNA clusters within the imprinted Dlk1-Dio3 region on chromosome 14, which is regulated by DNA methylation and histone acetylation [39]. As a consequence, the expression of both miRNAs can be restored by the treatment of cancer cells with the DNA methyltransferase inhibitor 5-aza-2 -deoxycytidine or the histone deacetylase inhibitors phenylbutyrate (PBA) and trichostatin A, indicating that epigenetic alterations account for dysregulation of miR-127-3p and miR-376a-3p independent from the type of cancer [40,41].…”

Section: Discussionmentioning

confidence: 99%

Tumor Suppressor Function of miR-127-3p and miR-376a-3p in Osteosarcoma Cells

Fellenberg

Lehner

Saehr

et al. 2019

Cancers

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Since the introduction of high-dose chemotherapy about 35 years ago, survival rates of osteosarcoma patients have not been significantly improved. New therapeutic strategies replacing or complementing conventional chemotherapy are therefore urgently required. MicroRNAs represent promising targets for such new therapies, as they are involved in the pathology of multiple types of cancer, and aberrant expression of several miRNAs has already been shown in osteosarcoma. In this study, we identified silencing of miR-127-3p and miR-376a-3p in osteosarcoma cell lines and tissues and investigated their role as potential tumor suppressors in vitro and in vivo. Transfection of osteosarcoma cells (n = 6) with miR-127-3p and miR-376a-3p mimics significantly inhibited proliferation and reduced the colony formation capacity of these cells. In contrast, we could not detect any influence of miRNA restoration on cell cycle and apoptosis induction. The effects of candidate miRNA restoration on tumor engraftment and growth in vivo were analyzed using a chicken chorioallantoic membrane (CAM) assay. Cells transfected with mir-127-3p and miR-376a-3p showed reduced tumor take rates and tumor volumes and a significant decrease of the cumulative tumor volumes to 41% and 54% compared to wildtype cells. The observed tumor suppressor function of both analyzed miRNAs indicates these miRNAs as potentially valuable targets for the development of new therapeutic strategies for the treatment of osteosarcoma.

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“…Previous studies have identified several direct targets of miR-376a, including SP1 (16) in glioblastoma multiform, p85α (17) and H3K18 (30) in hepatocellular carcinoma, frizzled-4 in prostate cancer (18), c-Myc (19) in non-small-cell lung cancer, Krueppel-like factor 15 (29) and Caspase-8 (29) in ovarian cancer. SATB1, which is a cell type-specific nuclear matrix attachment region binding protein, was a direct target gene of miR-376a in OS.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑376a inhibits cell proliferation and invasion in osteosarcoma via directly targeting SATB1

Guang-hong

Jiang

2018

Mol Med Report

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Aberrantly expressed microRNAs (miRs) are implicated in the regulation of osteosarcoma (OS) onset and development. Therefore, key miRs in OS must be identified to develop promising and effective therapeutic targets for patients with OS. In the present study, reverse transcription‑quantitative polymerase chain reaction analysis revealed that miR‑376a‑3p expression was downregulated in OS tissues and cell lines. Additionally, decreased miR‑376a expression was associated with tumor size and lymph node infiltration. Restoration of miR‑376a expression reduced cell proliferation and invasion of OS. Furthermore, special AT‑rich sequence‑binding protein 1 (SATB1) was identified as a direct target gene of miR‑376a in OS cells. Furthermore, SATB1 was overexpressed in OS tissues and SATB1 overexpression was inversely correlated with the expression level of miR‑376a. In addition, ectopic SATB1 expression counteracted the inhibitory effects of miR‑376a overexpression on the proliferation and invasion of OS cells. All these results identified that reduced miR‑376a expression may be implicated in the mechanism underlying OS progression, suggesting that the miR‑376a/SATB1 axis may be a promising novel target for potential therapeutic methods for the effective treatment of patients with OS.

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MiR-376a and Histone Deacetylation 9 Form A Regulatory Circuitry in Hepatocellular Carcinoma

Cited by 34 publications

References 29 publications

MicroRNA-873 Promotes Cell Proliferation, Migration, and Invasion by Directly Targeting TSLC1 in Hepatocellular Carcinoma

MicroRNA-873 Promotes Cell Proliferation, Migration, and Invasion by Directly Targeting TSLC1 in Hepatocellular Carcinoma

Tumor Suppressor Function of miR-127-3p and miR-376a-3p in Osteosarcoma Cells

MicroRNA‑376a inhibits cell proliferation and invasion in osteosarcoma via directly targeting SATB1

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