HDAC6 regulates microRNA-27b that suppresses proliferation, promotes apoptosis and target MET in diffuse large B-cell lymphoma

Jia, Yanjing; Liu, Z B; Wang, W G; Sun, Chuanyu; Wei, Ping; Yang, Ya‐Ling; You, M. James; Yu, Bo; Li, X Q; Zhou, Xiang

doi:10.1038/leu.2017.299

Cited by 50 publications

(43 citation statements)

References 52 publications

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“…A recent study has shown that activated transcription factor 3 in association with HDAC6 acts to decrease the transcription of miR‐199a‐2/miR‐214 . HDAC6 also negatively regulates miR‐27b through Rel A/p65 to modulate the MET/PI3K/AKT pathway in diffusing large B‐cell lymphoma . Based on these reports, we hypothesized that loss or suppression of HDAC6, as a potent histone modifier, causes re‐activation of comprehensive functional RNAs, especially oncogenic microRNAs (oncomiRs), and thereby suppresses tumor suppressors contributing to hepatocellular carcinogenesis.…”

mentioning

confidence: 98%

HDAC6 Suppresses Let‐7i‐5p to Elicit TSP1/CD47‐Mediated Anti‐Tumorigenesis and Phagocytosis of Hepatocellular Carcinoma

Yang

Kim

et al. 2019

Hepatology

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Histone deacetylase 6 (HDAC6) uniquely serves as a tumor suppressor in hepatocellular carcinogenesis, but the underlying mechanisms leading to tumor suppression are not fully understood. To identify comprehensive microRNAs (miRNAs) regulated by HDAC6 in hepatocellular carcinogenesis, differential miRNA expression analysis of HDAC6transfected Hep3B cells was performed. Using integrative analyses of publicly available transcriptome data and miRNA target prediction, we selected five candidate miRNAs and, through in vitro functional validation, showed that let-7i-5p specifically suppressed thrombospondin-1 (TSP1) in hepatocellular carcinoma (HCC). Ectopic expression of antisense let-7i-5p (AS-let-7i-5p) inhibited in vitro tumorigenesis of HCC cells. In addition, treatments of partially purified TSP1 from culture cell media (ppTSP1) and recombinant TSP1 (rTSP1) exhibited similar effects with AS-let-7i-5p treatment on the same HCC cells, whereas TSP1 neutralizing antibody treatment significantly attenuated these effects. Notably, treatments of HDAC6 plasmid, AS-let-7i-5p, ppTSP1, and rTSP1 significantly suppressed in vitro angiogenesis and metastatic potential of HCC cells, but the co-treatment of TSP1 antibody specific to cluster of differentiation 47 (CD47) binding domain successfully blocked these effects in the same cells. Furthermore, we demonstrated that recovery of HDAC6 elicited let-7i-5p suppression to de-repress TSP1 expression; therefore, it occupied the CD47 receptor to block CD47-SIRPα-mediated anti-phagocytosis of macrophage in HCC. We also observed that HCC-derived exosomal let-7i-5p suppressed TSP1 of recipient hepatocyte cells. Treatments of HDAC6 plasmid, AS-let-7i-5p, and rTSP1 suppressed tumor incidence as well as tumor growth rates in a spontaneous mouse HCC model. Conclusion: Our findings suggest that the HDAC6-let-7i-5p-TSP1 regulatory pathway suppresses neoplastic and antiphagocytic behaviors of HCC by interacting with cell surface receptor CD47 in HCC and neighboring cells of tumor microenvironment, providing a therapeutic target for the treatment of liver malignancy and metastasis. (Hepatology 2019;70:1262-1279).H epatocellular carcinoma (HCC) is an aggressive form of cancer, the fifth most common cancer and the third leading cause of cancer death worldwide. (1) However, the overall survival of patients with HCC has not improved significantly over the past two decades, and the mechanisms

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confidence: 98%

HDAC6 Suppresses Let‐7i‐5p to Elicit TSP1/CD47‐Mediated Anti‐Tumorigenesis and Phagocytosis of Hepatocellular Carcinoma

Yang

Kim

et al. 2019

Hepatology

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“…At the molecular level, miR-155 represses the growth-inhibitory effects of bone morphogenetic protein receptor type 2 (BMPR2) and TGF-β in DLBCL cells via direct targeting of SMAD5 [ 180 ], and, in a therapeutic view, ectopic delivery of anti-miR-155 leads to lymphoma regression in a xeno-transplant mouse model [ 181 ]. Recently it was shown that an increased expression of miR-27b , by the histone deacetylase 6 (HDAC6) knockdown, inhibits tumor growth in a DLBCL mouse model, by targeting the MET proto-oncogene, receptor tyrosine kinase (MET)/phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (PIK3CB, also known as PI3K)/AKT oncogenic pathway (MET/PI3K/AKT) [ 182 ]. MiR-26a and miR-181a also display oncosuppressor features.…”

Section: Mirnas In Hematological Malignanciesmentioning

confidence: 99%

MicroRNAs in Autoimmunity and Hematological Malignancies

Marco

Ramassone

Pagotto

et al. 2018

IJMS

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Autoimmunity and hematological malignancies are often concomitant in patients. A causal bidirectional relationship exists between them. Loss of immunological tolerance with inappropriate activation of the immune system, likely due to environmental and genetic factors, can represent a breeding ground for the appearance of cancer cells and, on the other hand, blood cancers are characterized by imbalanced immune cell subsets that could support the development of the autoimmune clone. Considerable effort has been made for understanding the proteins that have a relevant role in both processes; however, literature advances demonstrate that microRNAs (miRNAs) surface as the epigenetic regulators of those proteins and control networks linked to both autoimmunity and hematological malignancies. Here we review the most up-to-date findings regarding the miRNA-based molecular mechanisms that underpin autoimmunity and hematological malignancies.

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“…Accumulating evidence suggested that miRs may be important in the development of malignancies (6). Previous studies demonstrated that miRs are involved in a number of cancer cell biological processes, including metastasis (7), invasion (8), angiogenesis (9), proliferation, apoptosis (10), differentiation (11), metabolism (12) and drug resistance (13). The dysregulation of miRs is observed in the majority of types of cancer, including RCC (14).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑222‑3p promotes tumor cell migration and invasion and inhibits apoptosis, and is correlated with�an�unfavorable prognosis of patients with renal cell carcinoma

Zhao

Quan

et al. 2018

Int J Mol Med

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The aim of the present study was to investigate the role of microRNA (miR)-222-3p in renal cell carcinoma (Rcc). The expression level of miR-222-3p was detected in Rcc tissues and cell lines (AcHN, 786-O, caki-1 and 769-P) and was identified to be significantly upregulated compared with the level in adjacent normal renal tissues and HK-2 cells. Further in vitro experiments demonstrated that the over expression of miR-222-3p promoted the migration and invasion, and attenuated the apoptosis of 786-O cells, whereas the knockdown of miR-222-3p suppressed the migration and invasion and induced the apoptosis of 786-O cells. Similar results were observed in the ACHN cell line in terms of migration, invasion and apoptosis. Furthermore, the expression level of miR-222-3p was measured in 42 RCC formaldehyde-fixed paraffin-embedded samples, and the association between the expression of miR-222-3p and the pathological characteristics and overall survival rate of patients with Rcc was analyzed. The results demonstrated that patients with a higher expression of miR-222-3p had a significantly lower overall survival rate, compared with those with a lower expression of miR-222-3p [hazard ratio (HR)=5.120; P=0.036]. Multivariate analysis identified that patients with a higher expression of miR-222-3p retained the statistically significant decrease in overall survival rate compared with patients with a lower expression of miR-222-3p (HR=5.636; P=0.030). Furthermore, Kaplan-Meier survival curves indicated that patients with higher miR-222-3p had significantly lower overall survival rates compared with patients with lower miR-222-3p (P=0.020). Taken together, these results suggested that miR-222-3p serves as an onco-miR in RCC and may be a potential prognostic biomarker and therapeutic target in patients with RCC.

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HDAC6 regulates microRNA-27b that suppresses proliferation, promotes apoptosis and target MET in diffuse large B-cell lymphoma

Cited by 50 publications

References 52 publications

HDAC6 Suppresses Let‐7i‐5p to Elicit TSP1/CD47‐Mediated Anti‐Tumorigenesis and Phagocytosis of Hepatocellular Carcinoma

HDAC6 Suppresses Let‐7i‐5p to Elicit TSP1/CD47‐Mediated Anti‐Tumorigenesis and Phagocytosis of Hepatocellular Carcinoma

MicroRNAs in Autoimmunity and Hematological Malignancies

MicroRNA‑222‑3p promotes tumor cell migration and invasion and inhibits apoptosis, and is correlated with�an�unfavorable prognosis of patients with renal cell carcinoma

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