Tripartite motif-containing 54 promotes gastric cancer progression by upregulating K63-linked ubiquitination of filamin C.

BACKGROUND: Tripartite motif (TRIM) proteins have been proved to contribute to cancer progression, while whether tripartite motif-containing 54 (TRIM54) could functionally influence gastric cancer (GC) progression remains elusive. METHODS: The expression level of TRIM54 and filamin C (FLNC) in GC was determined by Western blot and online database. Cell Counting Kit-8 (CCK-8) assay, colony formation assay and Ethylenediurea (EdU) staining were performed to explore the effects of TRIM54 on GC cell proliferation. Transwell assay and wound healing assay were applied to detect the influence of TRIM54 on GC cell migration and invasion. Bioinformatics analysis and Co-immunoprecipitation assay (Co-Ip), Ubiquitination assay and Half-life assay were involved to explore the regulatory mechanism of TRIM54 on FLNC. RESULTS: TRIM54 was upregulated in GC tissues and cells, and a higher expression level of TRIM54 indicated a shorter overall survival of GC patients. The overexpression of TRIM54 significantly enhanced proliferation, migration, and invasion of GC cells, and inhibition of TRIM54 expression exerted reverse effects on GC cells. Mechanistically, TRIM54 was determined as a post-translational mediator of FLNC, and TRIM54 was co-immunoprecipitated with FLNC and degraded its protein level via K63-linked ubiquitination of FLNC. Notably, FLNC efficiently inhibited GC progression by TRIM54 overexpression. CONCLUSION: Collectively, our findings suggested that the TRIM54/FLNC axis could be considered as a potential prognostic biomarker for GC.

Clinical significance and prognostic value of SOX7 expression in liver and pancreatic carcinoma.

Sex determining region Y­box 7 (SOX7) is known to function as a tumor suppressor in a number of types of cancer; however, its role in liver and pancreatic carcinoma remains unclear. The present study investigated the association between SOX7 expression and the clinical pathology of these carcinomas, in particular if SOX7 expression may be used to predict recurrence and patient prognosis following radical resection of liver and pancreatic carcinoma. SOX7 expression in human liver and pancreatic carcinoma was detected by immunohistochemical analyses and validated using mRNA data from a high­throughput sequencing dataset from The Cancer Genome Atlas (TCGA). SOX7 expression was significantly downregulated in liver and pancreatic carcinoma relative to the adjacent benign tissues [immunoreactivity scores: Liver carcinoma (3.53±1.57) vs. benign (7.00±0.00), P<0.001; and pancreatic carcinoma (2.39±1.88) vs. benign (4.80±0.45), P=0.005]. In addition, downregulation of SOX7 was significantly associated with advanced stage liver carcinoma, and the primary pathological tumor stage and regional lymph node stages. These findings were further validated in the TCGA dataset. However, SOX7 down regulation was closely associated with the only pathological grade in pancreatic patients. Kaplan­Meier analyses revealed significant differences in overall and disease­free survival between patients with high and low levels of SOX7 expression. In addition, a multivariate analysis with Cox regression indicated that SOX7 may be an independent predictor of disease­free survival. The results indicate that SOX7 may inhibit the progression of liver carcinoma and that SOX7 downregulation may accurately predict poor prognosis in liver carcinoma patients.

Mastermind-like Transcriptional Coactivator 1 Overexpression Predicts Poor Prognosis in Human with Hepatocellular Carcinoma.

BACKGROUND: Mastermind-like transcriptional coactivator 1(MAML1) is a transcriptional coregulator of activators in various signaling pathways. High MAML1 was associated with tumorigenesis, progression, and aggressiveness in various tumors. The role of MAML in Hepatocellular Carcinoma (HCC), however, has not been directly addressed. The present study was to determine its association with clinicopathological characteristics and prognosis of HCC patients. MATERIALS AND METHODS: MAML1 expression at protein level in human HCC and normal liver tissues was detected by immunohistochemistry analysis, which was further validated by high-throughput sequencing data TCGA dataset at mRNA level. Then, the association of MAML1 expression with clinicopathological features of HCC patients was statistically analyzed. RESULTS: Immunohistochemistry analysis found that MAML1 expression was significantly increased in HCC tissues compared with those in normal tissues (P=0.005). High MAML1 was dramatically associated with advanced clinical stage (P=0.019) and enhanced tumor invasion (P=0.019). The TCGA mRNA expression data showed that MAML1 was upregulated in HCC with young age (P=0.005). Kaplan-Meier survival curves revealed that HCC patients with high MAML1 levels had shorter survival (P=0.040). Furthermore, high MAML1 expression was an independent prognostic factor for HCC patients (HR 1.841, 95% CI 1.045-3.243; P=0.035). CONCLUSIONS: Our data suggests that MAML1 may play an important role in tumor progression of HCC. The increased expression of MAML1 may efficiently predict poor overall survival in HCC patients, and it may be a potential prognostic marker of this malignancy.