Downregulation of TNFRSF19 and RAB43 by a novel miRNA, miR-HCC3, promotes proliferation and epithelial-mesenchymal transition in hepatocellular carcinoma cells.

Tumor necrosis factor receptor superfamily 19 (TNFRSF19) is a transmembrane protein involved in tumorigenesis. RAB43 is a small molecule GTP-binding protein contributing to the occurrence and development of tumors. However, TNFRSF19/RAB43 dysregulation and their role in hepatocellular carcinoma cells are unknown. Herein, we found that TNFRSF19 and RAB43 were downregulated in hepatocellular carcinoma tissues. TNFRSF19/RAB43 overexpression suppressed, whereas TNFRSF19/RAB43 knockdown promoted cell proliferation and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma cells. Previously, using deep sequencing technology, a new miRNA, miR-HCC3, was identified and found to suppress the expression of TNFRSF19 and RAB43 by binding to their 3'untranslated regions (3'UTRs) directly. miR-HCC3 was upregulated in hepatocellular carcinoma (HCC) tissues compared with adjacent noncancerous tissues and promoted proliferation and epithelial-mesenchymal transition in HCC cells. Furthermore, TNFRSF19/RAB43 suppressed but miR-HCC3 promoted tumor growth in vivo. Collectively, our results indicated that downregulation of TNFRSF19 and RAB43 by miR-HCC3 contributes to oncogenic activities in HCC, which sheds light on tumorigenesis and might provide potential therapeutic targets for HCC.

Verteporfin enhances the sensitivity of LOVO/TAX cells to taxol via YAP inhibition.

Studies have reported that taxol (TAX) is an effective drug for the treatment of colorectal cancer; however, its application inevitably results in drug resistance. Overexpression of Yes-associated protein (YAP) is considered one of the factors that cause TAX resistance, which may be inhibited by verteporfin (VP) treatment. The present study aimed to confirm the role of YAP in TAX resistance and to investigate whether the drug sensitivity of the TAX-resistant LOVO/TAX cell line to TAX is affected by VP treatment. The role of YAP in TAX resistance was first determined through vector-mediated overexpression and inhibition of YAP in cells. Reverse-transcription quantitative polymerase chain reaction and western blot analysis were performed for detection of associated mRNA and protein, respectively. An MTT assay was used to detect the drug sensitivity of cells to TAX. The results suggested that compared with that in the native LOVO cell line, YAP expression was significantly increased in LOVO/TAX cells. YAP gene silencing markedly enhanced the drug sensitivity of LOVO/TAX cells to TAX and, on the contrary, the drug sensitivity notably declined when YAP was overexpressed in LOVO cells. The results indicated that YAP gene expression and TAX resistance were correlated. VP treatment suppressed YAP expression and increased the drug sensitivity of LOVO/TAX cells to TAX in a dose-dependent manner. In addition, compared with VP alone, VP and TAX combination therapy had a greater inhibitory effect on YAP expression. VP treatment enhanced the drug sensitivity of LOVO/TAX cells to TAX through inhibiting YAP expression.

[Effects of different gracilis loops in graciloplasty on congenital fecal incontinence].

OBJECTIVE: To compare the clinical effect of graciloplasty using two different gracilis encircled loops and to research the better method for the treatment of fecal incontinence after anoplasty for imperforate anus. METHODS: Clinical data of 38 incontinence patients with congenital anal malformation undergoing graciloplasty in our hospitals from January 2009 to January 2012 were retrospectively analyzed. Twenty patients received the modified surgery in which the gracilis muscle was transposed anticlockwise into a circum-anal tunnel with a U-loop and its tendon secured to the ipsilateral pectineal ligament. Eighteen patients received the traditional surgery in which the gracilis muscle was wrapped clockwise around the anus with a γ-loop and its tendon secured to the contralateral periosteum of ischial tuberosity or pectineal ligament. All the patients were evaluated via Wexner score and anal manometry before surgery and 2 weeks, 6 months, 1 year and 2 years after surgery. In addition, it was assessed whether the patients had difficulty defecating while squatting after surgery. RESULTS: Generalized estimating equations showed that the Wexner score in two groups gradually decreased after surgery (P=0.000), but there was no significant difference between two groups (P=0.554). At 2 weeks, 6 months, 1 year and 2 years after surgery, there were respectively 4 cases (20.0%), 3 cases (15.0%), 2 cases (10.0%), 1 case (5.0%), who showed squatting difficult defecation in the U-loop group, and 10 cases (55.6%), 12 cases (66.7%), 10 cases (55.6%), 8 cases (44.4%) in the γ-loop group. The probability of squatting difficult defecation in U-loop group was significantly lower compared to γ-loop group (P=0.002), but the probability of squatting difficult defecation in two groups did not obviously change with time (P=0.057). Repeated measures ANOVA showed that anal resting pressure, anal maximal squeeze pressure, duration of anal squeeze, and rectal maximum tolerable volume in two groups were gradually improved after surgery (all P<0.01), but there were no significant differences between two groups (all P>0.05). CONCLUSIONS: Graciloplasty with different gracilis loops can improve anal function. However, U-loop can better improve difficult defecating while squatting, and is worthwhile for spreading in clinical practice.

[Expression of vasohibin-1 in colorectal cancer tissue and its correlation with vascular endothelial growth factor A and microvessei density].

OBJECTIVE: To explore the clinical significance of vasohibin-1 expression in colorectal cancer tissues and its correlation with vascular endothelial growth factor A(VEGF-A) and microvessel density (MVD). METHODS: Tumor tissues and paired adjacent normal tissue (distance to cancer >5 cm) from 60 colorectal cancer patients undergoing resection in the Second Hospital of Tianjin Medical University from June 2013 to November 2013 were included in this study. The protein expressions of vasohibin-1, VEGF-A and MVD were detected by immunohistochemical staining. The mRNA expressions of vasohibin-1 and VEGF-A were detected by RT-PCR. The protein expressions of vasohibin-1 and VEGF-A were observed by Western blot. Correlation among parameters was examined. RESULTS: Vasohibin-1 expression was mainly localized in the cytoplasm of tumor cells and endothelial cells. VEGF-A expression was mainly localized in the cytoplasm and membrane of tumor cells. The expressions of vasohibin-1, VEGF-A and MVD in colorectal tumor tissues were significantly higher than those in corresponding adjacent tissues [43.3% (26/60) vs. 16.7% (10/60), 51.7%(31/60) vs. 18.3% (11/60), (39.67 ± 16.80)/mm² vs. (17.85 ± 6.43)/mm², all P<0.05]. Higher vasohibin-1 expression was significantly associated with TNM stage and metastasis (P<0.05). Vasohibin-1 expression was positively correlated with VEGF-A and MVD (r=0.378, 0.628, all P<0.05). Vasohibin-1 and VEGF-A mRNA expressions and protein expressions in colorectal cancer tissues were significantly higher than those in corresponding adjacent tissues (all P<0.05). CONCLUSION: Vasohibin-1 expression in colorectal cancer tissues is significantly higher as compared to corresponding adjacent tissues. Vasohibin-1 expression is positively correlated to VEGF-A and MVD, and associated to TNM stage and metastasis. Positive vasohibin-1 expression indicates a poor prognosis of patients with colorectal cancer.

[Diagnosis and treatment of sacrococcygeal teratoma in adults: analysis of 17 cases].

OBJECTIVE: To investigate the diagnosis and treatment of sacrococcygeal teratoma in adults. METHODS: The clinical data of 17 patients with sacrococcygeal teratoma confirmed by pathological examination, 9 males and 8 females, aged 20 - 53, were analyzed retrospectively. RESULT: Correct diagnosis was made pre-operatively in 13 of the 17 patients. Two cases were misdiagnosed as with leiomyoma, and 2 cases as with sacrococcygeal cyst. Pathological examination confirmed the diagnosis of teratoma in all 17 cases. Thirteen patients were followed up for 1 - 5 years post-operatively. Malignant change was seen in 1 case, and 1 patient died 1 year after operation. Two patients suffered a relapse and then fully recovered after re-operation, and the other 15 patients all recovered without relapse. CONCLUSION: Sacrococcygeal teratoma in adults usually has no typical clinical symptom and signs and is often misdiagnosed. The pathologic examination is the base to make a definite diagnosis. Complete excision is necessary to prevent local recurrence and potential malignant transformation. The sacrococcygeal approach or combined abdominal-sacral approach is recommended.