MiR-4262 promotes cell apoptosis and inhibits proliferation of colon cancer cells: involvement of GALNT4.

A role of microRNA-4262 (miR-4262) in the carcinogenesis of colon cancer remains undetermined. In this study, we studied the effects and mechanisms of miR-4262 to the colon cancer cell proliferation and apoptosis. We found that the levels of miR-4262 significantly down-regulated in colon cancer tissue, compared to the paired adjacent non-tumor colon tissue. The miR-4262 levels in colon cancer cell lines were significantly lower than those in control normal colon tissues. Transfection with the miR-4262 mimic decreased the cell proliferation and increased cell apoptosis in colon cancer cells, while transfection with the antisense of miR-4262 (as-miR-4262) increased cell proliferation and suppressed cell apoptosis in colon cancer cells. Bioinformatics analyses showed that GALNT4 was a potential target gene of miR-4262. The luciferase activities assay and Western blot verified that miR-4262 targeted GALNT4 mRNA to modulate its protein levels. When we treated cells with miR-4262 and GALN4 siRNA, the cell viability was significantly decreased. Together, our study suggests that aberrantly expressed miR-4262 may affect cell apoptosis and proliferation of human colon cancer cells via GALNT4, which appears to be a promising therapeutic target for colon cancer.

[Value of adrenal venous sampling in the subtype diagnosis of primary aldosteronism].

OBJECTIVE: To assess the diagnostic value of adrenal venous sampling (AVS) in the subtype diagnosis of primary aldosteronism (PA). METHODS: The diagnosis of PA was made in 36 patients based on an elevated ratio of plasma aldosterone (ALD) to plasma rennin activity (PRA) (ARR) and confirmed tests (saline infusion or captopril challenge) in recent 3 years. All PA patients underwent adrenal computed tomographic scan (CT) and AVS. The diagnostic accuracy of CT and AVS in the subtype differentiation of PA were evaluated by comparing the differences of CT findings, AVS results and clinical outcomes. RESULTS: Fifteen of 36 patients (42%) had a final diagnosis of aldosterone-producing adenoma (APA) and another 21 patients (58%) with bilateral adrenal hyperplasia (BAH). The level of ALD was significantly higher in APA group than that in BAH group (298.9 ± 91.0 vs 226.3 ± 59 ng/L, P < 0.05). PRA (ng×ml(-1)×h(-1)) in APA patients were markedly lower than that in BAH counterparts (0.18 ± 0.14 vs 0.28 ± 0.29 ng×ml(-1)×h(-1), P < 0.01). Consequently, ARR in APA group was evidently higher than that in BAH group (2444.7 ± 1405.2 vs 1550.0 ± 1059.8, P < 0.05). Plasma potassium in APA patients was lower than that in those with BAH (2.71 ± 0.57 vs 3.17 ± 0.40 mmol/L). But there was no statistic significance (P > 0.05). The CT findings were discordant with the AVS results in 27.8% of patients (10/36). The accuracy of adrenal CT scan was only 72.2% in the subtype diagnosis of PA, provided AVS was the gold standard for distinguishing between APA and BAH. Reliance on CT findings could lead to inappropriate management in 25% of PA patients. Conversely, the AVS results were concordant with the clinical outcomes in 94.4% of all patients. CONCLUSION: CT scan is not a reliable method of differentiating primary aldosteronism. Compared with CT, AVS is more accurate in establishing a correct diagnosis of primary aldosteronism. AVS should be performed routinely before operation in PA patients opting for adrenalectomy.

[Effects of mesenchymal stem cell transplantation on growth of liver cancer: experiment with rats].

OBJECTIVE: To evaluate the effects of mesenchymal stem cell (MSC) transplantation on the growth of liver cancer. METHODS: MSCs were isolated from the bone marrows of SD rats. Walker-256 cancer cells were isolated from the cancerous ascites of rat and cultured. Forty-five SD rats were randomly divided into 3 equal groups: mixed transplantation group undergoing laparotomy and transplantation of cancer cells mixed with MSCs into the liver, MSC IV transplantation group undergoing injection of MSCs into the caudal vein, and control group undergoing only MSC transplantation into the liver. MR imaging was performed s at days 3, 6, 9 and 12 after modeling to measure the maximum cross section area of the tumor. At day 12 the rats were killed after MR imaging with their livers taken out to undergo HE staining and pathological examination. Immunohistochemistry was used to detect the expression of vascular endothelial cell growth factors (VEGF), nm23 gene, a tumor metastasis inhibiting gene, and proliferating cell nuclear antigen (PCNA), a nuclear polypeptide necessary in the DNA synthesis. RESULTS: No significant evidence of tumor formation was detected by MRI at days 3 and 6 after modeling in all rats and tumor nodules were observed since day 9. The maximum cross section areas of tumor of the mixed transplantation group and MSC IV transplantation group were significantly larger than that of the control group at days 9 and 12 (F = 4.21, P < 0.05; F = 8.52, P < 0.01). Immunohistochemistry showed that VEGF expression levels of the two study groups were both significantly higher than that of the control group (F = 9.58, P < 0.01), while the nm23 gene expression levels of the 2 study groups were both significantly lower than that of the control group (F = 4.61, P < 0.05). The PCNA expression level of the mixed transplantation group was significantly higher than that of the control group (d'((1, 0.05)) = 0.34, d'((1, 0.01)) = 0.63, P < 0.05), however, there was no significant difference in the PCNA expression level between the MSCs IV transplantation group and the control group (d'((1, 0.05)) = 0.32, d'((1, 0.01)) = 0.48, P > 0.05). There was no significant difference in the tumor apoptotic index between the 2 study groups and the control group (F = 1.25, P > 0.05). CONCLUSION: MSC transplantation increases the expression of VEGF and PCNA, while decreases the expression of nm23 gene in cancer cells, thus favoring the tumor growth.