miR-4443 targets TRIM14 to suppress metastasis and energy metabolism of papillary thyroid carcinoma (PTC) in vitro.

Tripartite motif-containing protein 14 (TRIM14) is a tumor-promoter in papillary thyroid carcinoma (PTC). We found that miR-4443 expression was significantly downregulated in PTC tumor tissue, and was negatively associated with TRIM14. This study was designed to investigate the relationship between miR-4443 and TRIM14 on metastasis and energy metabolism in PTC and the underlying mechanisms. To this end, human PTC cells (SW1736 and MZ-CRC-1) were transfected with a miR-4443 mimic or miR-4443 inhibitor + siRNA-TRIM14, and then dual-luciferase assay, Transwell, Seahorse, and western blot analyses were performed to assess the function of miR-4443 and the underlying mechanism. We found that ectopic expression of miR-4443 inhibited PTC cell migration, invasion, ATP production, and aerobic glycolysis, while inhibition of miR-4443 had the opposite effect. miR-4443 directly targeted TRIM14 and reduced both TRIM14 mRNA and protein levels. Silencing TRIM14 significantly reversed miR-4443 inhibition-induced PTC cell migration, invasion, ATP production, aerobic glycolysis, and phosphorylation of the transcription factor STAT3. These findings suggest that miR-4443 is a tumor suppressor in PTC and inhibits metastasis and energy metabolism via the suppression of TRIM14 signaling.

Are ADC values of readout-segmented echo-planar diffusion-weighted imaging (RESOLVE) correlated with pathological prognostic factors in rectal adenocarcinoma?

BACKGROUND: Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) values as imaging biomarkers of rectal cancer are currently a hot research spot. The use of ADC values for preoperative judgment of pathological features in rectal cancer has been generally accepted. The image quality evaluation of conventional diffusion is severe deformation, and the measurement of ADC values can easily lead to bias. Readout-segmented echo-planar diffusion-weighted imaging (RESOLVE) provides high signal-to-noise ratio images and significantly reduces distortions caused by magnetosensitive effects. The purpose of this study was to explore the correlations between ADC values of RESOLVE and pathological prognostic factors in rectal adenocarcinoma. METHODS: We collected pathological data of 89 patients with pathologically confirmed rectal adenocarcinoma who directly underwent surgical resection without receiving adjuvant therapy. The patients were grouped according to the pathologic type, gross classification, degree of differentiation, TN stage, and immunohistochemical expression of epidermal growth factor receptor (EGFR). RESULTS: RESOLVE ADC values of rectal cancer were measured at b = 800, and correlations between the RESOLVE ADC values obtained in different groups were analysed. We found that RESOLVE ADC values in the ulcer-type group were significantly higher than those in the eminence-type group. CONCLUSION: RESOLVE ADC values in different pathologic types of rectal cancer were significantly different. RESOLVE ADC values in the EGFR-positive group were significantly lower than those in the EGFR-negative group. There was no significant difference in RESOLVE ADC values between different degrees of pathologic differentiation, TN stages, and positive or negative lymph nodes. The quantitative description of RESOLVE ADC values could be used to assess the biological behaviour of rectal adenocarcinoma.

The mitochondrial nucleoid protein, Mgm101p, of Saccharomyces cerevisiae is involved in the maintenance of rho(+) and ori/rep-devoid petite genomes but is not required for hypersuppressive rho(-) mtDNA.

The Saccharomyces cerevisiae MGM101 gene encodes a DNA-binding protein targeted to mitochondrial nucleoids. MGM101 is essential for maintenance of a functional rho(+) genome because meiotic segregants, with a disrupted mgm101 allele, cannot undergo more than 10 divisions on glycerol medium. Quantitative analysis of mtDNA copy number in a rho(+) strain carrying a temperature-sensitive allele, mgm101-1, revealed that the amount of mtDNA is halved each cell division upon a shift to the restrictive temperature. These data suggest that mtDNA replication is rapidly blocked in cells lacking MGM101. However, a small proportion of meiotic segregants, disrupted in MGM101, have rho(-) genomes that are stably maintained. Interestingly, all surviving rho(-) mtDNAs contain an ori/rep sequence. Disruption of MGM101 in hypersuppressive (HS) strains does not have a significant effect on the propagation of HS rho(-) mtDNA. However, in petites lacking an ori/rep, disruption of MGM101 leads to either a complete loss or a dramatically decreased stability of mtDNA. This discriminatory effect of MGM101 suggests that replication of rho(+) and ori/rep-devoid rho(-) mtDNAs is carried out by the same process. By contrast, the persistence of ori/rep-containing mtDNA in HS petites lacking MGM101 identifies a distinct replication pathway. The alternative mtDNA replication mechanism provided by ori/rep is independent of mitochondrial RNA polymerase encoded by RPO41 as a HS rho(-) genome is stably maintained in a mgm101, rpo41 double mutant.

MicroRNA-10b is upregulated and has an invasive role in colorectal cancer through enhanced Rhoc expression.

We found that the difference in miR­10b expression between the tumor tissue and adjacent non­tumor tissue was significant. Outer periphery and portal vein serum miR­10b concentrations were significantly higher than those of the control. However, the outer periphery vein miR­10b concentrations were not significant when compared with the portal vein serum concentration in colorectal cancer. The expression levels of miR­10b were associated with higher­grade colorectal cancer. MiR­10b levels were markedly elevated in lymph node metastasis-positive tumor tissue compared with those in lymph node metastasis-free tumor tissue, and were correlated with a downregulation in Hoxd10 expression. Rhoc protein expression in tumor tissue was significantly amplified when compared to that of the control tissue group. An inverse correlation between Hoxd10 and Rhoc in immunohistochemistry and western blot analysis was observed (P<0.05). MiR-10b expression was also inversely correlated with Hoxd10 protein expression (P<0.05). Thus, miR­10b is potentially involved in the invasion of colorectal cancer.