Overexpression of SET and MYND Domain-Containing Protein 2 (SMYD2) Is Associated with Tumor Progression and Poor Prognosis in Patients with Papillary Thyroid Carcinoma

Abstract

BackgroundsSET and MYND domain-containing protein 2 (SMYD2), which is identified as a protein-lysine methyltransferase, plays a crucial role in the progression of some tumors such as bladder carcinoma. However, the clinical significance of SMYD2 in patients with papillary thyroid carcinoma (PTC) has not been elucidated. In the present study, we aimed to investigate the expression and role of SMYD2 in human PTC.Material/MethodsClinicopathological analysis was performed in 107 patients with PTC. Expression of SMYD2 was determined by immunohistochemistry staining, quantitative RT-PCR, or Western blotting in PTC tissues, adjacent normal tissues, and PTC cells (K1 and B-CPAP). The prognostic value of SMYD2 in PTC patients was assessed by univariate and multivariate analysis. Clinical outcomes were evaluated by Kaplan-Meier log-rank tests. Cell proliferation was examined in PTC cells following overexpression or knockdown of SMYD2.ResultsSMYD2 was highly expressed in PTC tissues compared to adjacent thyroid tissues. Additionally, high expression of SMYD2 was significantly related to tumor size, lymph node metastasis, and TNM stage. Moreover, SMYD2 was identified as an independent prognosis factor by multivariate analysis. Using 2 PTC cell lines, K1 and B-CPAP, we demonstrated that high expression of SMYD2 can promote tumor cell proliferation.ConclusionsSMYD2 expression was upregulated in PTC tissues and significantly related to the poorer prognosis of PTC patients. Our studies suggested the potential role of SMYD2 as a new therapeutic target and prognostic biomarker in human PTC.

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

“…RNA expression profiles were analyzed by real-time PCR using iTaq SYBR Green Super-mix with ROX (BioRad) in an icycleriQTM Real-time PCR detection system. SMYD2-OE and MDR1 transcripts were amplified using primers described previously 22,23…”

Histone methyltransferase SMYD2: ubiquitous regulator of disease

“…In addition, SMYD2 is also overexpressed in gastric cancer [66], pancreatic ductal adenocarcinoma (PDAC) [43], papillary thyroid carcinoma [80], hepatocellular carcinoma [81], and colon cancer [82]. Furthermore, overexpression of SMYD2 protein positively correlates with larger tumor size, more aggressive lymphatic invasion, deeper tumor invasion, and higher TNM stage, as well as worse overall survival rate [80, 81]. Multiple nonhistone proteins are methylated by SMYD2 to achieve these effects on tumors, for example, MAPKAPK3 in PDAC and ALK in non-small-cell lung cancer (NSCLC) [43, 44].…”

Comprehensive analysis of aberrantly expressed long non‑coding RNAs, microRNAs, and mRNAs associated with the competitive endogenous RNA network in cervical cancer

“…Previous studies have shown that cBX7 is a vital tumor suppressor, and the absence of cBX7 contributes to tumorigenesis, whereas high expression of cBX7 is correlated with longer survival time (47,48). High expression of SMYD2 was found in papillary thyroid carcinoma and hepatocellular carcinoma tissues, and patients with papillary thyroid cancer and hepatocellular cancer with upregulated SMYd2 were observed to have poor disease outcomes (49,50). Consistent with our findings, luo et al (51) suggested that the expression of the mrna LATS2 was a significant predictive factor of overall survival in lung adenocarcinoma.…”