MiR-2861 Behaves as a Biomarker of Lung Cancer Stem Cells and Regulates the HDAC5-ERK System Genes

Zhao, Mingxia; Lin, Li; Zhou, Jundong; Cui, Xueyuan; Tian, Qingmei; Jin, Yaqing; Zhu, Y.

doi:10.1089/cell.2017.0045

Cited by 15 publications

(9 citation statements)

References 37 publications

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“…miR-2861 overexpression has previously reported to be associated with PTC metastasis (27). Other studies have indicated that miR-2861 is involved in the development of lung and cervical cancer (28,29). The present results indicate that miR-2861 is upregulated in PTC tissues compared with that in adjacent normal tissues, also suggesting that miR-2861 may serve as an oncogene in PTC.…”

Section: Primer (5'-3') ---------------------------------------------supporting

confidence: 68%

lncRNA DGCR5 acts as a tumor suppressor in papillary thyroid carcinoma via sequestering miR‑2861

Chen¹,

Yin

Zhu³

et al. 2018

Exp Ther Med

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A vast amount of evidence indicates that long non-coding RNAs (lncRNAs) are involved in cancer. Previous studies have indicated that lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) is aberrantly expressed in lung cancer, pancreatic ductal adenocarcinoma and hepatocellular carcinoma. However, the role of DGCR5 in papillary thyroid carcinoma (PTC) has remained elusive. In the present study, it was revealed that DGCR5 was significantly downregulated in PTC tissues compared with that in adjacent normal tissues. Through functional experiments, it was demonstrated that ectopic overexpression of DGCR5 markedly suppressed PTC cell growth and invasion. A bioinformatics analysis suggested that DGCR5 binds to microRNA (miR)-2861. A total of 5 putative binding sites for miR-2861 were identified in DGCR5, and a luciferase reporter assay confirmed the direct interaction between DGCR5 and miR-2861. Furthermore, reverse transcription-quantitative polymerase chain reaction analysis indicated that ectopic overexpression of DGCR5 led to a decreased expression of miR-2861 in PTC cells and miR-2861 mimic transfection caused a downregulation of DGCR5. miR-2861 level was upregulated in PTC tissues compared with adjacent tissues and negatively correlated with DGCR5 level. In addition, rescue experiments indicated that ectopic expression of miR-2861 reversed the effects of DGCR5 overexpression on PTC cell proliferation and invasion. Taken together, the present results demonstrated that DGCR5 inhibits PTC progression via sponging miR-2861, indicating DGCR5 may serve as a therapeutic target.

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Section: Primer (5'-3') ---------------------------------------------supporting

confidence: 68%

lncRNA DGCR5 acts as a tumor suppressor in papillary thyroid carcinoma via sequestering miR‑2861

Chen¹,

Yin

Zhu³

et al. 2018

Exp Ther Med

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“…LMK-235, a novel HDAC class IIA HDACi specifically inhibiting HDAC5 (IC 50 = 4.22 nM) and HDAC4 (IC 50 = 11.9 nM), was found to be cytotoxic in several human cancer cell lines [ 31 ]. Relating to the mechanisms of LMK-235’s cytotoxic action, studies performed on lung cancer cells indicate that HDAC5 inhibition with LMK-235 interferes with the ERK-1/2 pathway involved in the differentiation of cancer stem cells [ 32 ]. Recently, Li et al identified Bcl-2-associated transcription factor 1 (BCLAF1) as a potential epigenetic therapeutic target involved in LMK-235-mediated apoptosis in diffuse large B-cell lymphoma cells [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Inhibition of Class IIA HDACs by LMK-235 in Pancreatic Neuroendocrine Tumor Cells

Wanek

Gaisberger

Beyreis

et al. 2018

IJMS

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Histone deacetylases (HDACs) play a key role in epigenetic mechanisms in health and disease and their dysfunction is implied in several cancer entities. Analysis of expression patterns in pancreatic neuroendocrine tumors (pNETs) indicated HDAC5 to be a potential target for future therapies. As a first step towards a possible treatment, the aim of this study was to evaluate the in vitro cellular and molecular effects of HDAC5 inhibition in pNET cells. Two pNET cell lines, BON-1 and QGP-1, were incubated with different concentrations of the selective class IIA HDAC inhibitor, LMK-235. Effects on cell viability were determined using the resazurin-assay, the caspase-assay, and Annexin-V staining. Western Blot and immunofluorescence microscopy were performed to assess the effects on HDAC5 functionality. LMK-235 lowered overall cell viability by inducing apoptosis in a dose- and time-dependent manner. Furthermore, acetylation of histone-H3 increased with higher LMK-235 concentrations, indicating functional inhibition of HDAC4/5. Immunocytochemical analysis showed that proliferative activity (phosphohistone H3 and Ki-67) decreased at highest concentrations of LMK-235 while chromogranin and somatostatin receptor 2 (SSTR2) expression increased in a dose-dependent manner. HDAC5 expression was found to be largely unaffected by LMK-235. These findings indicate LMK-235 to be a potential therapeutic approach for the development of an effective and selective pNET treatment.

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“…HDAC5 showed elevated expression in tumorspheres formed by H460 lung cancer cells. Application of the HDAC5 inhibitor LMK-235 reduced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in a dose-dependent manner, demonstrating that the HDAC5-ERK1/2 axis plays an important role in maintaining the stemness of lung cancer stem cells ( 93 ). Additionally, during ovarian cancer (OC) progression, HDAC5 interacted with YY1 to promote OC cell stemness by deacetylating the promoter of the microRNA miR-99a ( 64 ).…”

Section: Hdac5 In Cancermentioning

confidence: 99%

Insights Into the Function and Clinical Application of HDAC5 in Cancer Management

Yang

Gong

et al. 2021

Front. Oncol.

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Histone deacetylase 5 (HDAC5) is a class II HDAC. Aberrant expression of HDAC5 has been observed in multiple cancer types, and its functions in cell proliferation and invasion, the immune response, and maintenance of stemness have been widely studied. HDAC5 is considered as a reliable therapeutic target for anticancer drugs. In light of recent findings regarding the role of epigenetic reprogramming in tumorigenesis, in this review, we provide an overview of the expression, biological functions, regulatory mechanisms, and clinical significance of HDAC5 in cancer.

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MiR-2861 Behaves as a Biomarker of Lung Cancer Stem Cells and Regulates the HDAC5-ERK System Genes

Cited by 15 publications

References 37 publications

lncRNA DGCR5 acts as a tumor suppressor in papillary thyroid carcinoma via sequestering miR‑2861

lncRNA DGCR5 acts as a tumor suppressor in papillary thyroid carcinoma via sequestering miR‑2861

Pharmacological Inhibition of Class IIA HDACs by LMK-235 in Pancreatic Neuroendocrine Tumor Cells

Insights Into the Function and Clinical Application of HDAC5 in Cancer Management

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