RNA methyltransferase NSUN2 promotes gastric cancer cell proliferation by repressing p57Kip2 by an m5C-dependent manner.

The RNA methyltransferase NSUN2 has been involved in the cell proliferation and senescence, and is upregulated in various types of cancers. However, the role and potential mechanism of NSUN2 in gastric cancer remains to be determined. Our study showed that NSUN2 was significantly upregulated in gastric cancers, compared to adjacent normal gastric tissues. Moreover, NSUN2 could promote gastric cancer cell proliferation both in vitro and in vivo. Further study demonstrated that CDKN1C (p57Kip2) was the potential downstream gene of regulated by NSUN2 in gastric cancer. NSUN2 could promote gastric cancer cell proliferation through repressing p57Kip2 in an m5C-dependent manner. Our findings suggested that NSUN2 acted as an oncogene through promoting gastric cancer development by repressing p57Kip2 in an m5C-dependent manner, which may provide a novel therapeutic target against gastric cancer.

The optimum marker for the detection of lymphatic vessels.

Podoplanin, lymphatic vessel endothelial hyaluronic acid receptor-1, prospero-related homeobox-1 and vascular endothelial growth factor receptor 3 have been demonstrated to have crucial roles in the development of the lymphatic system and lymphangiogenesis process by combining with their corresponding receptors. Thus, the four markers have been widely used in labelling lymphatic vessels for the detection of lymphangiogenesis and lymphatic vessel invasion. Numerous authors have aimed to identify the roles of these four markers in the lymphatic system and the mechanisms have been partly clarified at the molecular level. The aim of the present review was to comprehensively clarify the characteristics and latent action modes of the four markers in order to determine which is the best one for the detection of lymphangiogenesis and lymphatic vessel invasion.

Expression of insulin-like growth factor binding protein-2 in gastric carcinoma and its relationship with cell proliferation.

AIM: To investigate the expression of insulin-like growth factor binding protein-2 (IGFBP-2) in gastric carcinoma and its clinical significance and to explore its relationship with cell proliferation. METHODS: Expressions of IGFBP-2 and Ki-67 in 118 cases of gastric carcinoma and 40 cases of normal gastric mucosa were detected by EnVision immunohistochemical technique. RESULTS: Expression of IGFBP-2 in gastric carcinoma was higher than that in normal gastric mucosa (P < 0.01). There was no difference between high- and low-grade gastric carcinoma (P > 0.05). Expression of IGFBP-2 in advanced gastric carcinoma was higher than that in early gastric carcinoma (P < 0.05). Expression of IGFBP-2 in gastric carcinoma with lymph node metastasis was higher than that without lymph node metastasis (P < 0.01). IGFBP-2 expression was a positively related to the clinical stage of gastric carcinoma (P < 0.01). There was a positive correlation between IGFBP-2 and Ki-67 (P < 0.05). CONCLUSION: IGFBP-2 may be involved in carcino-genesis and progression of gastric carcinoma by promoting cell proliferation.

Relationship between inactivation of p16 gene and gastric carcinoma.

AIM: To investigate the relationship between inactivation of p16 gene and gastric carcinoma, and the mechanism of inactivation of p16 gene in gastric carcinogenesis. METHODS: 40 fresh tumor tissue specimens were taken from primary gastric cancer patients. Expression of P16 protein was detected by immunohistochemical method. Deletion and point mutation of p16 gene were analyzed by polymerase chain reaction (PCR) and DNA sequencing, respectively. RESULTS: The frequency of loss of P16 protein expression in the gastric cancer tissue, adjacent nontumor tissue, and distal normal tissue was 77.5 % (31/40), 55.0 % (22/40), and 17.5 % (7/40), respectively (P<0.005). Homozygous deletion of exon 1 and exon 3 was observed in two and three cases, respectively, giving an overall frequency of homozygous deletion of 12.5 %. All five cases had diffuse type gastric carcinoma. No p16 gene point mutation was detected. CONCLUSION: These findings suggest a close correlation between inactivation of p16 gene and gastric carcinoma. Further investigations are needed to testify the mechanism of inactivation of p16 gene in gastric carcinogenesis.

Heparanase mRNA expression and point mutation in hepatocellular carcinoma.

AIM: To explore the expression of heparanase mRNA and point mutation in hepatocellular carcinoma (HCC). METHODS: Reverse transcription polymerase chain reaction was used to measure the expression of heparanase mRNA in the primary tumor tissues and surrounding liver tissues of 33 HCC patients. T-A cloning and sequencing were used to detect whether there was any mutation in the amplified PCR products. RESULTS: The expression of heparanase mRNA was positive in 16 primary tumor tissues of HCC, and the positive rate was 48.5%, which was significantly higher than that in the surrounding liver parenchyma (P<0.01). The positive rate for heparanase gene in high-tendency to metastatic recurrence group (71.4%, 10/14) was obviously higher than that in low-tendency to metastatic recurrence group (31.6%, 6/19) (P = 0.023). The positive rate for heparanase gene in patients with metastatic recurrence during postoperative follow-up (78.6%, 11/14) was also significantly higher than that in those without metastatic recurrence (21.4%, 3/14) (P = 0.003). Sequence analysis of the HPA PCR products was made in 7 patients, and 2-point mutations were found in 4 patients, one of which was sense mutation, neither base insertion nor deletion was detected. The mutation rate was 57.1% (4/7). CONCLUSION: The expression rate of heparanase mRNA increases in HCC, and HPA mRNA may be one of the reliable markers for the metastatic activity gained by the liver tumor cells and could be used clinically in predicting metastatic recurrence of HCC. Point mutation may be one of the causes for enhanced heparanase mRNA expression.

[Expression of mucin MUC1 and MUC2 in colorectal carcinoma and their clinical significance].

BACKGROUND & OBJECTIVE: The up-regulation of mucin MUC1 expression or down-regulation of mucin MUC2 expression may be involved in carcinogenesis of some neoplasms, but there was few report about the relationship between mucin MUC1 and MUC2 expression and Chinese colorectal carcinoma. The aim of this study was to explore relationship between expression of mucin MUC1 and MUC2 in colorectal carcinoma and clinicopathological parameters and their clinical significance. METHODS: The expression of mucin MUC1 and MUC2 in 126 cases of colorectal carcinoma were detected by S-P immunohistochemical technique. RESULTS: The positive expression rates of mucin MUC1 and MUC2 in normal colorectal mucosa were 0 and 100%, respectively, but the positive expression rates of mucin MUC1 and MUC2 in 126 cases of colorectal carcinoma were 42.1% and 36.5%, respectively (P < 0.01); the expression of mucin MUC1 was positive correlated to the depth of invasion, lymph node metastasis, and Dukes staging (P < 0.05), but negative correlated to the degree of differentiation (P < 0.05); mucin MUC2 expression was related to invasion, lymph node metastasis, and Dukes staging (P < 0.05), but unrelated to differentiation (P > 0.05). CONCLUSIONS: The up-regulation of mucin MUC1 expression or down-regulation of mucin MUC2 expression may be involved in carcinogenesis and progression in colorectal carcinoma, and the detecting of mucin MUC1 and MUC2 may be predicting its prognosis in colorectal carcinoma.