miR-326-Histone Deacetylase-3 Feedback Loop Regulates the Invasion and Tumorigenic and Angiogenic Response to Anti-cancer Drugs

Kim, Youngmi; Kim, Hyuna; Park, Hyunmi; Park, Deokbum; Lee, Hansoo; Lee, Yun Sil; Choe, Jongseon; Kim, Young Myeong; Jeoung, Dooil

doi:10.1074/jbc.m114.578229

Cited by 43 publications

(53 citation statements)

References 48 publications

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“…Moreover, HDAC3 and p53 have been shown to interact indirectly via formation of a complex with the MAGE-A tumour antigen, which confers resistance to chemotherapeutic agents 9 . In accordance with the above finding, downregulation of HDAC3 decreases cancer cell death in response to anticancer drugs 10 . Stimuli such as osmotic stress or FAS ligand binding trigger the caspase-7-dependent C-terminal cleavage of HDAC3 in mammalian cells, eventually leading to apoptosis induction by modulation of HDAC3 activity 11 12 .…”

supporting

confidence: 86%

Programmed cell death 5 mediates HDAC3 decay to promote genotoxic stress response

Choi

Park

et al. 2015

Nat Commun

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The inhibition of p53 activity by histone deacetylase 3 (HDAC3) has been reported, but the precise molecular mechanism is unknown. Here we show that programmed cell death 5 (PDCD5) selectively mediates HDAC3 dissociation from p53, which induces HDAC3 cleavage and ubiquitin-dependent proteasomal degradation. Casein kinase 2 alpha phosphorylates PDCD5 at Ser-119 to enhance its stability and importin 13-mediated nuclear translocation of PDCD5. Genetic deletion of PDCD5 abrogates etoposide (ET)-induced p53 stabilization and HDAC3 cleavage, indicating an essential role of PDCD5 in p53 activation. Restoration of PDCD5WT in PDCD5−/− MEFs restores ET-induced HDAC3 cleavage. Reduction of both PDCD5 and p53, but not reduction of either protein alone, significantly enhances in vivo tumorigenicity of AGS gastric cancer cells and correlates with poor prognosis in gastric cancer patients. Our results define a mechanism for p53 activation via PDCD5-dependent HDAC3 decay under genotoxic stress conditions.

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supporting

confidence: 86%

Programmed cell death 5 mediates HDAC3 decay to promote genotoxic stress response

Choi

Park

et al. 2015

Nat Commun

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“…It has been reported that multiple lncRNAs in the SNHG family, such as SNHG1 and SNHG5, can sponge miRNAs to regulate their expression in different cancers, including prostate cancer and gastric cancer, thus participating in the tumor growth (Li et al 2017;Zhao et al 2017). In addition, miR-326 has been demonstrated to inhibit the growth of various types of tumors including HCC (Kim et al 2014;Li et al 2015b;Cao et al 2016;Wu et al 2017;Zhang et al 2017;Yin et al 2018). However, the relationship between SNHG3 and miR-326 in HCC remains unclear.…”

Section: Discussionmentioning

confidence: 99%

LncRNA SNHG3 Promotes Hepatocellular Tumorigenesis by Targeting miR-326

Zhao

Wang

et al. 2019

Tohoku J. Exp. Med.

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Small nucleolar RNA host gene 3 (SNHG3), a long noncoding RNA (lncRNA), acts as an oncogene in hepatocellular carcinoma (HCC), whereas microRNA (miR)-326 plays an inhibitory role in some types of human cancers, including melanoma, osteosarcoma, and gastric cancer. In the present study, by analyzing 47 tissue specimens of human HCC, we found that the relative expression levels of SNHG3 were significantly higher in HCC tissues than those in the adjacent noncancerous tissues, whereas the relative expression levels of miR-326 were significantly lower in HCC tissues. Furthermore, the relative mRNA levels of Sma and Mad Related Family 3 (SMAD3) and zinc finger E-box binding homeobox 1 (ZEB1) were significantly higher in HCC tissues compared with the adjacent noncancerous tissues. In human HCC cell lines, SNHG3 overexpression promoted the proliferation, migration, and epithelial-mesenchymal transition and inhibited apoptosis, whereas knockdown of SNHG3 expression exerted the opposite effects. Importantly, miR-326 or miR-326 inhibitor restored the aforementioned effects of SNHG3 overexpression or SNHG3 knockdown. We thus found that the miR-326-response element is present in SNHG3 and the 3'-untranslated region of SMAD3 mRNA. In fact, SNHG3 overexpression increased the expression levels of SMAD3 and ZEB1, while miR-326 decreased the expression levels of SMAD3. These results suggest that SNHG3 may function as a competing endogenous RNA (ceRNA) for miR-326, which in turn enhances SMAD3 and ZEB1 expression. In conclusion, we propose that SNHG3 promotes HCC progression via the miR-326/SMAD3/ZEB1 signaling pathway. The findings may provide novel targets for the diagnosis and treatment of HCC.

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“…Conventional Western blot analysis was performed following the methods described in a previous study [20]. The primary antibodies used included anti-Snail (1: 500, ab82846, Abcam, Cambridge, UK), anti-Vimentin (1: 2000, ab92547, Abcam) anti-E-cadherin (1: 1000, ab77287, Abcam), anti-slug (1: 1000, ab27568, Abcam), anti-P-gp (1: 2000, ab129450, Abcam), and anti-β-actin (1: 2000, ab8227, Abcam).…”

Section: Methodsmentioning

confidence: 99%

MiR-30a Decreases Multidrug Resistance (MDR) of Gastric Cancer Cells

Zou

Guo

et al. 2016

Med Sci Monit

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BackgroundThe effectiveness of chemotherapy for gastric cancer is largely limited by either intrinsic or acquired drug resistance. In this study, we aimed to explore the association between miR-30a dysregulation and multidrug resistance (MDR) in gastric cancer cells.Material/MethodsWe recruited 20 patients with advanced gastric cancer. Chemosensitivity was assessed after completion of the chemotherapy. SGC-7901 and SGC-7901/DDP cells were transfected for miR-30a overexpression or knockdown. Then, MTT assay was performed to assess the IC50 of DPP and 5-FU in SGC-7901 and SGC-7901/DDP cells. Flow cytometry analysis was used to detect DPP- and 5-FU-induced cell apoptosis. Western blot analysis and immunofluorescence staining were used to assess EMT of the cells.ResultsMiR-30a was significantly downregulated in the chemoresistant tissues. In both SGC-7901 and SGC-7901/DDP cells, miR-30a overexpression decreased the expression of P-gp, a MDR-related protein. MTT assay and flow cytometry analysis showed that miR-30a inhibition increased chemoresistance, while miR-30a overexpression decreased chemoresistance in gastric cancer cells. Both Western blot analysis and immunofluorescence staining confirmed that miR-30a inhibition decreased E-cadherin but increased N-cadherin in SGC-7901 cells, while miR-30a overexpression increased E-cadherin but decreased N-cadherin in SGC-7901 cells.ConclusionsMiR-30a can decrease multidrug resistance (MDR) of gastric cancer cells. It is also an important miRNA modulating EMT of the cancer cells.

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miR-326-Histone Deacetylase-3 Feedback Loop Regulates the Invasion and Tumorigenic and Angiogenic Response to Anti-cancer Drugs

Cited by 43 publications

References 48 publications

Programmed cell death 5 mediates HDAC3 decay to promote genotoxic stress response

Programmed cell death 5 mediates HDAC3 decay to promote genotoxic stress response

LncRNA SNHG3 Promotes Hepatocellular Tumorigenesis by Targeting miR-326

MiR-30a Decreases Multidrug Resistance (MDR) of Gastric Cancer Cells

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