&lt;p&gt;SMYD2-OE promotes oxaliplatin resistance in colon cancer through MDR1/P-glycoprotein via MEK/ERK/AP1 pathway&lt;/p&gt;

Ren, Haitao; Wang, Zheng; Chen, Yao; Liu, Yanjun; Zhang, Shu; Zhang, Tongtong; Li, Yuntao

doi:10.2147/ott.s186806

Cited by 22 publications

(16 citation statements)

References 33 publications

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“…Accumulating evidence has indicated that SMYD2 is associated with the drug resistance in several cancers, including non-small cell lung cancer, renal cell carcinoma and colon cancer (Ren et al, 2019;Shang and Wei, 2019;Yan et al, 2019). Our results showed that the inhibition of SMYD2 could significantly increase the sensitivity of chemo drugs in glioma cells.…”

Section: Discussionsupporting

confidence: 52%

STUB1-SMYD2 Axis Regulated Drug Resistance in Glioma cells

Pan

Wang

et al. 2021

Preprint

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Aim: SMYD2 is an important epigenetic regulator that methylates histone and non-histone proteins. This study aims to investigate SMYD2 as an oncogene of gliomas and explore its degradation mechanism induced by cisplatin.Methods: Tumor tissue microarray of 441 glioma patients was collected for SMYD2 immunohistochemistry staining. Kaplan-Meier survival curves were constructed by using he overall survival. mRNA-sequencing analysis was detected for understanding the downstream mechanisms mediated by SMYD2. The half-inhibitory concentrations (IC50) of temozolomide and cisplatin in AZ505-treated and control cells were calculated. Thepotential E3 ubiquitin ligase of SMYD2 was predicted in UbiBrowser and confirmed by knockdown test. The effect of SMYD2 and its E3 ligase on gliomas apoptosis and migration were determined via cell-function assays.Results: High SMYD2 expression correlated with a high WHO stage (P=0.004) and a low survival probability (P=0.012). The inhibition of SMYD2 suppressed the process of EMT by downregulating the expression of COL1A1. AZ505 treatment significantly increased drug sensitivity of glioma cells. And the expression of SMYD2 was markedly reduced by cisplatin treatment via STUB1 mediated degradation. The knockdown of STUB1 could partly reverse the cell function impairment induced by cisplatin.Conclusion: These findings suggested that SMYD2 could be a potential drug target for the treatment of gliomas, and STUB1-mediated degradation of SMYD2 plays an important role in reversing chemotherapy resistance in gliomas.

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Section: Discussionsupporting

confidence: 52%

STUB1-SMYD2 Axis Regulated Drug Resistance in Glioma cells

Pan

Wang

et al. 2021

Preprint

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“…SMYD2 was identified as a methyltransferase that methylates several key cancer-involved proteins, including retinoblastoma, p53, MAPKAPK3, and STAT3, to promote cancer development [ 5 , 8 , 21 , 32 ]. SMYD2-regulated cell proliferation is amongst these mechanisms that was reported in various types of cancers, for instance, colon cancer [ 9 , 35 ]. However, a recent study using small molecule inhibitors and CRISPR/Cas9 technology targeting SMYD2 in hundreds cancer cell lines questioned the functional role of SMYD2 in tumor cell proliferation [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

SMYD2 targets RIPK1 and restricts TNF-induced apoptosis and necroptosis to support colon tumor growth

Thonn

Patankar

et al. 2022

Cell Death Dis

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SMYD2 is a histone methyltransferase, which methylates both histone H3K4 as well as a number of non-histone proteins. Dysregulation of SMYD2 has been associated with several diseases including cancer. In the present study, we investigated whether and how SMYD2 might contribute to colorectal cancer. Increased expression levels of SMYD2 were detected in human and murine colon tumor tissues compared to tumor-free tissues. SMYD2 deficiency in colonic tumor cells strongly decreased tumor growth in two independent experimental cancer models. On a molecular level, SMYD2 deficiency sensitized colonic tumor cells to TNF-induced apoptosis and necroptosis without affecting cell proliferation. Moreover, we found that SMYD2 targeted RIPK1 and inhibited the phosphorylation of RIPK1. Finally, in a translational approach, pharmacological inhibition of SMYD2 attenuated colonic tumor growth. Collectively, our data show that SMYD2 is crucial for colon tumor growth and inhibits TNF-induced apoptosis and necroptosis.

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“…The PMT SMYD2 12 , 14 , 30 , as an oncogene, is closely connected with transcriptional regulation, epigenetics, and tumorigenesis 31 , 32 . SMYD2 is highly expressed and related to poor prognosis in multiple cancers, including BC 11 , esophageal squamous cell carcinoma 10 , acute lymphoblastic leukemia 12 , gastric cancer 9 , hepatocellular carcinoma 33 , and colon cancer 34 . In our study, we found that SMYD2 expression was upregulated in sample datasets procured from online databases, as well as in LUAD cell lines and tissues.…”

Section: Discussionmentioning

confidence: 99%

SMYD2 promotes tumorigenesis and metastasis of lung adenocarcinoma through RPS7

Kou

et al. 2021

Cell Death Dis

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The protein methyltransferase SET and MYND domain-containing protein 2 (SMYD2) is a transcriptional regulator that methylates histones and nonhistone proteins. As an oncogene, SMYD2 has been investigated in numerous types of cancer. However, its involvement in lung cancer remains elusive. The prognostic value of SMYD2 expression in lung adenocarcinoma (LUAD) was determined through bioinformatics analysis, reverse-transcription polymerase chain reaction, western blotting, and immunohistochemistry. The effect of SMYD2 on LUAD cell proliferation and metastasis was explored in vivo and in vitro, and the underlying mechanisms were investigated via RNA-seq, and chromatin immunoprecipitation-quantitative PCR. SMYD2 expression was significantly upregulated in LUAD cell lines and tissues. High SMYD2 expression was associated with shorter overall and disease-free survival in LUAD patients. Inhibition of SMYD2 with SMYD2 knockdown or AZ505 dramatically inhibited the proliferation, migration, and invasion ability of GLC-82 and SPC-A1 cells and remarkably reduced tumor growth in mice. Mechanically, SMYD2 may activate the transcription of ribosomal small subunit protein 7 (RPS7) by binding to its promoter. Following overexpression of SMYD2, the proliferation, migration, and invasion of cells increased, which was partially reversed by RPS7. Thus, SMYD2 might modulate tumorigenesis and metastasis mediated by RPS7 LUAD. SMYD2 might be a prognostic biomarker and therapeutic target in LUAD.

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<p>SMYD2-OE promotes oxaliplatin resistance in colon cancer through MDR1/P-glycoprotein via MEK/ERK/AP1 pathway</p>

Cited by 22 publications

References 33 publications

STUB1-SMYD2 Axis Regulated Drug Resistance in Glioma cells

STUB1-SMYD2 Axis Regulated Drug Resistance in Glioma cells

SMYD2 targets RIPK1 and restricts TNF-induced apoptosis and necroptosis to support colon tumor growth

SMYD2 promotes tumorigenesis and metastasis of lung adenocarcinoma through RPS7

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