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Tripartite Motif 14 (TRIM14) is an oncoprotein that belongs to the E3 ligase TRIM family, which is involved in the progression of various tumors except for non-small cell lung carcinoma (NSCLC). However, little is currently known regarding the function and related mechanisms of TRIM14 in NSCLC. Here, we found that the TRIM14 protein was downregulated in lung adenocarcinoma tissues compared with the adjacent tissues, which can suppress tumor cell proliferation and migration both in vitro and in vivo. Moreover, TRIM14 can directly bind to glutamine fructose-6-phosphate amidotransferase 1 (GFAT1), which in turn results in the degradation of GFAT1 and reduced O -glycosylation levels. GFAT1 is a key enzyme in the rate-limiting step of the hexosamine biosynthetic pathway (HBP). Replenishment of N -acetyl- d -glucosamine can successfully reverse the inhibitory effect of TRIM14 on the NSCLC cell growth and migration as expected. Collectively, our data revealed that TRIM14 suppressed NSCLC cell proliferation and migration through ubiquitination and degradation of GFAT1, providing a new regulatory role for TRIM14 on HBP. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect and mechanism of p-hydroxycinnamaldehyde (CMSP) momomer compounds extract from the Cochinchina momordica seeds on the growth and metastasis of melanoma transplanted tumors in mice with in vivo and in vitro experiments. Methods: A tumor-bearing mouse model was established, and 18 C57BL/6 mice were randomly divided into 3 groups (6 mice in each group): a control group (intraperitoneal injection of 0.1 ml normal saline) and two CMSP treatment groups (intraperitoneal injection of 1 and 2 mg/ml CMSP of 0.1 ml). From the 5th day of drug administration, the transplanted tumor in mice was measured with calipers and the volume was calculated before each administration. At the end of the experiment, the mass of transplanted tumor was weighed. The pathological changes of liver tissues were observed under light microscope after H-E staining. The expressions of E-cadherin and vimentin in the transplanted tumor tissues were detected by SP immunohistochemical method. The metastatic ability of melanoma B16 cells in the CMSP group (10, 20 µg/ml) was detected by cell scratch test and Transwell test after treatment for 24 and 48 h. The expressions of EMT-related mRNAs in B16 cells after treatment with CMSP for 24 h were detected by qPCR. The protein expression levels of β-catenin, p-β-catenin (Ser675), vimentin and E-cadherin in B16 cells treated with CMSP for 48 h were detected by Western blotting(WB). Results: The mean tumor volume and tumor mass of the mice in CMSP treatment group were significantly decreased (all P<0.05). The number of liver metastases in the control group was significantly higher than that in the CMSP (1 and 2 mg/ kg) groups (all P<0.05); moreover, no obvious metastases were found in the liver tissues of the 2 mg/kg CMSP treatment group. The expression level of E-cadherin protein in CMSP group (1 and 2 mg/kg) was significantly higher than that in the control group (all P<0.05), while the expression level of vimentin protein was significantly lower than that in the control group (all P<0.01). For the in vitro experiments, the scratch healing rate of B16 cells in CMSP groups (10, 20 µg/ml) after treatment for 24 and 48 h was significantly lower than that in control group (all P<0.05). The number of B16 cells passing through Transwell compartment in the 20 µg/ml CMSP treatment group was significantly decreased as compared with the control group (all P<0.01). The mRNA expression level of P-catenin in B16 cells treated with CMSP (10, 20 µg/ ml) was significantly lower than that in control group (all P<0.01), while the mRNA expression level of E-cadherin was significantly increased (all P<0.05); However, the mRNA expression level of vimentin in the 10 µg/ml treatment group was not significantly different from that in the control group (P>0.05), but it was significantly decreased in the 20 µg/ml treatment group (P<0.01). Compared with the control group, the protein expressions of β-catenin, p-β-catenin and vimentin in B16 cells of CMSP groups (10 and 20 µg/ml) were significantly decreased (all P<0.01), while the protein expression of E-cadherin was significantly increased (all P<0.01). Conclusion: CMSP can inhibit the growth and metastasis of melanoma transplanted tumors in mice, and its mechanism may be related to the activity of wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]

A substantial fraction of transcripts are known as long noncoding RNAs (lncRNAs), and these transcripts play pivotal roles in the development of cancer. However, little information has been published regarding the functions of lncRNAs in oesophageal squamous cell carcinoma (ESCC) and the underlying mechanisms. In our previous studies, we demonstrated that small nucleolar RNA host gene 5 (SNHG5), a known lncRNA, is dysregulated in gastric cancer (GC). In this study, we explored the expression and function of SNHG5 in development of ESCC. SNHG5 was found to be downregulated in human ESCC tissues and cell lines, and this downregulation was associated with cancer progression, clinical outcomes and survival rates of ESCC patients. Furthermore, we also found that overexpression of SNHG5 significantly inhibited the proliferation, migration and invasion of ESCC cells in vivo and in vitro. Notably, we found that metastasis-associated protein 2 (MTA2) was pulled down by SNHG5 in ESCC cells using RNA pulldown assay. We also found that SNHG5 reversed the epithelial–mesenchymal transition by interacting with MTA2. In addition, overexpression of SNHG5 downregulated the transcription of MTA2 and caused its ubiquitin-mediated degradation. Thus, overexpression of MTA2 partially abrogated the effect of SNHG5 in ESCC cell lines. Furthermore, we found that MTA2 mRNA expression was significantly elevated in ESCC specimens, and a negative correlation between SNHG5 and MTA2 expression was detected. Overall, this study demonstrated, for the first time, that SNHG5-regulated MTA2 functions as an important player in the progression of ESCC and provide a new potential therapeutic strategy for ESCC. [ABSTRACT FROM AUTHOR]