Overexpression of SMYD3 Is Predictive of Unfavorable Prognosis in Hepatocellular Carcinoma

Xiao, Fei; Ma, Yun; Liu, Xiaowei; Meng, Zhaohai

doi:10.1620/tjem.243.219

Cited by 21 publications

(14 citation statements)

References 22 publications

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“…SMYD3 protein expression levels appear to convey an unfavorable prognosis in HCC. In a cohort of 100 HCC cases, Fei et al showed that high SMYD3 expression correlated with HCC tumor size and poor overall survival [33]. In this study, patients with low expressing SMYD3 tumors had a 5-year overall survival rate of 48.7%, in contrast to the highly expressing SMYD3 group of 29.6%.…”

Section: Hepatocellular Carcinomamentioning

confidence: 49%

Clinicopathologic significance of protein lysine methyltransferases in cancer

et al. 2020

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Protein lysine methyltransferases (PKMTs) constitute a large family of approximately 50 chromatin modifiers that mono-, di- and/or tri-methylate lysine residues on histone and non-histone substrates. With the advent of The Cancer Genome Atlas, it became apparent that this family of chromatin modifiers harbors frequent genetic and expression alterations in multiple types of cancer. In this regard, past and ongoing preclinical studies have provided insight into the mechanisms of action of some of these enzymes, laying the ground for the ongoing development of PKMT inhibitors as novel anticancer therapeutics. The purpose of this review is to summarize existing data obtained by different research groups through immunohistochemical analysis of the protein expression levels of PKMTs, and their respective clinicopathologic associations. We focused on studies that used immunohistochemistry to associate protein expression levels of specific PKMTs, as well as several established histone methylation marks, with clinicopathologic features and survival outcomes in various cancer types. We also review ongoing clinical trials of PKMT inhibitors in cancer treatment. This review underscores the clinical relevance and potential of targeting the family of PKMT enzymes as the next generation of cancer therapy.

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Section: Hepatocellular Carcinomamentioning

confidence: 49%

Clinicopathologic significance of protein lysine methyltransferases in cancer

et al. 2020

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“…SMYD3 knockdown increases cisplatin sensitivity in tumor cells. SMYD3 is often highly expressed in cancer tissues and is closely associated with malignancy and poor prognosis of patients (29,30). However, the association between SMYD3 expression, chemotherapy and its outcomes remains unclear.…”

Section: Resultsmentioning

confidence: 99%

SET and MYND domain‑containing protein 3 inhibits tumor cell sensitivity to cisplatin

Wang

et al. 2020

Oncol Lett

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Cisplatin resistance has been a major factor limiting its clinical use as a chemotherapy drug. The present study aimed to investigate whether SET and MYND domain-containing protein 3 (SMYD3), a histone methyltransferase closely associated with tumors can affect the sensitivity of tumors to cisplatin chemotherapy. Real time-qPCR, western blotting, the luciferase reporter, MTT and clonogenic assays were performed to detect the effects of SMYD3 on the chemotherapy capacity of cisplatin. In the present study, SMYD3 exhibited different expression patterns in MCF-7 and T47D breast cancer cells. In addition, this differential expression was associated with tumor cell resistance to cisplatin. Furthermore, SMYD3 knockdown following small interfering RNA transfection increased cisplatin sensitivity, whereas SMYD3 overexpression decreased cisplatin sensitivity. In addition, SMYD3 knockdown synergistically enhanced cisplatin-induced cell apoptosis. SMYD3 expression was downregulated during cisplatin treatment. In addition, transcriptional regulatory activities of SMYD3 3'-untranslated region were also downregulated. These results suggested that SMYD3 may affect cell sensitivity to cisplatin and participate in the development of cisplatin resistance, which is a process that may involve microRNA-124-mediated regulation.

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“…In vitro evidence indicates that SMYD3 expression is up-regulated in HCC cell lines 12,32 . SMYD3 expression was analyzed in HCC tissues, and upregulation was significantly associated with an unfavourable prognosis of HCC 33,34 . SMYD3 mRNA expression was upregulated in HCC tumor compared to adjacent non-tumor tissues, providing further evidence of a role of SMYD3 in HCC development.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of SMYD3 and SMYD3 VNTR 3/3 polymorphism increase the risk of hepatocellular carcinoma

Binh

Hoàn

Giang

et al. 2020

Sci Rep

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SMYD3 (SET and MYND domain-containing protein 3) is involved in histone modification, which initiates oncogenesis by activating transcription of multiple downstream genes. To investigate associations of variable numbers of tandem repeats (VNTR) variants in the SMYD3 gene promoter, SMYD3 serum levels and SMYD3 mRNA expression in hepatitis B virus (HBV) infection and clinical progression of related liver disease. SMYD3VNTRs were genotyped in 756 HBV patients and 297 healthy controls. SMYD3 serum levels were measured in 293 patients and SMYD3 mRNA expression was quantified in 48 pairs of hepatocellular tumor and adjacent non-tumor liver tissues. Genotype SYMD3 VNTR 3/3 was more frequent among HCC patients than in controls (P adjusted = 0.037). SMYD3 serum levels increased according to clinical progression of liver diseases (P = 0.01); HCC patients had higher levels than non-HCC patients (P = 0.04). Among patients with SMYD3 VNTR 3/3, HCC patients had higher SMYD3 levels than others (P < 0.05). SMYD3 mRNA expression was up-regulated in HCC tumor tissues compared to other tissues (P = 0.008). In conclusion, upregulation of SMYD3 correlates with the occurrence of HCC and SMYD3 VNTR 3/3 appears to increase the risk of HCC through increasing SMYD3 levels. SMYD3 may be an indicator for HCC development in HBV patients.Although effective hepatitis B virus (HBV) vaccines are in use worldwide, HBV-related liver diseases are still a major health concern with approximately 257 million chronic infections and 887,000 deaths in 2015 1 . HBV is the main cause of primary hepatocellular carcinoma (HCC) 2 . The risk of HCC development is approximately 40 times higher in chronic HBV carriers (CHB) than in non-carriers 3 . Vietnam has a high prevalence of HBV infections, ranging from 10-20% in the general population and 20-40% among high-risk groups 2,4 . As a result, Vietnam is one of the countries with a high incidence of HCC with >25,000 new cases reported in 2018 5,6 .Further to viral factors contributing to cancer development, methylation of histone proteins is an important mechanism involved in multiple types of cancers including HCC 7,8 . Methylation of histone proteins at lysine residues can lead to chromatin remodelling, transcription, and signal transduction 9 . The SET and MYND domain containing proteins (SMYDs) belong to a family of the multi-domain SET-containing histone lysine methyltransferases and play a crucial role in histone methylation. To date, five SMYD family members have been recognized (SMYD1-SMYD5). SMYD3 is the most important member, as several findings have demonstrated its role in tumor cell growth and its increased expression in various cancers.SYMD3 promotes dimethylation and trimethylation of histone H3 lysine 4 (H3K4), which initiates oncogenesis by activating transcription of multiple downstream target genes 10,11 . SYMD3 overexpression causes cell proliferation, migration and adhesion, whereas suppression by RNAi inhibits cell proliferation and migration, indicating that SMYD3 plays an important role i...

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Overexpression of SMYD3 Is Predictive of Unfavorable Prognosis in Hepatocellular Carcinoma

Cited by 21 publications

References 22 publications

Clinicopathologic significance of protein lysine methyltransferases in cancer

Clinicopathologic significance of protein lysine methyltransferases in cancer

SET and MYND domain‑containing protein 3 inhibits tumor cell sensitivity to cisplatin

Upregulation of SMYD3 and SMYD3 VNTR 3/3 polymorphism increase the risk of hepatocellular carcinoma

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