SMYD3 overexpression was a risk factor in the biological behavior and prognosis of gastric carcinoma

Abstract

SET and MYND domain-containing protein 3 (SMYD3), a histone methyltransferase, plays a key function in the progression of human cancer. However, the role of SMYD3 in gastric carcinoma carcinogenesis has yet to be elucidated. This study aimed to determine the relationships of SMYD3 expression with clinicopathological characteristics and prognosis in gastric carcinoma. The expression of SMYD3 was detected by real-time quantitative reverse transcription PCR and Western blot in gastric carcinoma (GC) cell lines, normal gastric mucosa cell line, GC tissues, and adjacent non-tumor tissues. SMYD3 expression in tissue sections of 180 gastric carcinoma samples were evaluated using immunohistochemistry. The staining results were compared with clinicopathological characteristics and to the outcome of patients. The expression levels of SMYD3 messenger RNA (mRNA) and protein in GC tissues were both higher than those in adjacent non-tumor tissues (p < 0.05). SMYD3 mRNA and protein expression levels were higher in GC cell lines MKN28, SGC7901, and MGC803 than normal gastric mucosa cell line GES-1. SMYD3 expression in gastric carcinoma was significantly correlated with primary tumor size (p < 0.001), lymph node metastasis (p < 0.001), and TNM stage (p = 0.011). Degree of differentiation [hazard ratio (HR) = 5.113; p = 0.006], serosal invasion (HR = 2.074; p = 0.024), lymph node metastasis (HR = 1.354; p < 0.001), and SMYD3 expression (HR = 0.564; p = 0.004) were identified as the independent factors of the overall survival (OS) in all enrolled GC patients. For patients with positive lymph node metastasis, degree of differentiation (HR = 5.974; p = 0.015), lymph node metastasis (HR = 1.257; p < 0.001), and SMYD3 expression (HR = 0.529; p = 0.004) were the independent prognostic factors of the OS. SMYD3 performed an important function in the aggressiveness of gastric carcinoma and may act as a promising target for prognostic prediction.

SET and MYND domain-containing protein 3 is overexpressed in human glioma and contributes to tumorigenicity

“…We also demonstrated that SMYD3 overexpression increased glioma cell proliferation and promoted tumorigenesis in vitro, whereas SMYD3 knockdown by shRNA inhibited tumorigenesis. These data are consistent with a recent study that investigated the function of SMYD3 in gastric and breast cancers (26,27). All of these findings are supported by a recent study, which reported that the overexpression of SMYD3 protein in breast cancer alters tumor cell fate and promotes tumor progression (27).…”

Protein lysine methyltransferase SMYD3 is involved in tumorigenesis through regulation of HER2 homodimerization

“…SET and MYND domain‐containing protein 3 (SMYD3) is a protein lysine methyltransferase, and is overexpressed in a wide range of cancers, including breast, colorectal, hepatocellular, lung, and pancreatic carcinomas . Several lines of evidence have indicated that SMYD3 plays a pivotal role in human tumorigenesis through methylation of histone and nonhistone protein substrates . In this study, we demonstrated trimethylation of a lysine 175 residue of HER2 by SMYD3, which may affect the HER2 homodimerization and the activation of its downstream pathways.…”

“…As mentioned above, we and other groups reported that SMYD3 was highly expressed in various types of human cancer , and is implicated to have an oncogenic function . However, the biological significance of nonhistone protein methylation by SMYD3 has not been well characterized.…”

Effect of SMYD3 on the microRNA expression profile of MCF-7 breast cancer cells

“…SMYD3 is located on human chromosome 1 and encodes two protein isoforms that are composed of 428 and 369 amino acids. Previous studies have demonstrated that SMYD3 is frequently overexpressed in numerous types of cancer cells, including hepatic, colon, gastric and cervical carcinoma, and breast cancer (2)(3)(4), whilst the expression levels were lower in the corresponding normal tissue. A number of previous studies have demonstrated that SMYD3 has vital roles in the process of tumor development via its functions as a histone methylation enzyme and a transcription factor (5,6).…”