RESUMO
BACKGROUND: The purpose of this study was to investigate the role of hsa_circRNA_102051 in colorectal cancer (CRC) and its effect on the stemness of tumor cells. METHODS: CircRNA microarray was under analysis to screen differentially expressed novel circRNAs in the pathology of CRC. Quantitative real-time PCR was used to detect the relative RNA expression in CRC cells and samples. The effects of hsa_circRNA_102051 on biological functions in CRC cells were accessed both in vitro and in vivo. FISH, RIP and luciferase reporter assay were conducted to confirm the regulatory correlations between hsa_circRNA_102051 and miR-203a, as well as miR-203a and BPTF. Xenograft models were applied to further verify the impacts and fluctuations of hsa_circRNA_102051/miR-203a/BPTF. Moreover, the mechanism how hsa_circRNA_102051 affected the Notch signals was also elucidated. RESULTS: Hsa_circRNA_102051 was up-regulated in CRC tissues and cell lines, capable to promote the growth and invasion of CRC. In addition, hsa_circRNA_102051 could enhance stemness of CRC cells. BPTF was identified as downstream factors of hsa_circRNA_102051, and miR-203a was determined directly targeting both hsa_circRNA_102051 and BPTF as an intermediate regulator. Hsa_circRNA_102051 in CRC could block miR-203a expression, and subsequently activated BPTF. Hsa_circRNA_102051/miR-203a/BPTF axis modulated stemness of CRC cells by affecting Notch pathway. CONCLUSIONS: Our findings provided new clues that hsa_circRNA_102051 might be a potential predictive or prognostic factor in CRC, which induced the fluctuation of downstream miR-203a/BPTF, and subsequently influenced tumor growth, activities and stemness. Thereinto, the Notch signals were also involved. Hence, the hsa_circRNA_102051/miR-203a/BPTF axis could be further explored as a therapeutic target for anti-metastatic therapy in CRC patients.
RESUMO
The objective of the study was to investigate the clinicopathological features of primary colorectal signet-ring cell carcinoma. We retrospectively analyzed the clinical and survival data of 37 patients with primary colorectal signet-ring cell carcinoma. The mean survival time of patients in stage II, III, and IV were estimated using Student t test and the cumulative survival rates were estimated according to the method of Kaplan-Meier. The significance of the differences in survival rates were calculated using the log rank test. The incidence of primary colorectal signet-ring cell carcinoma was 1.40%, the median age of 37 patients was 50 years, the male to female ratio was 1.47:1, and 21 patients (56.8%) received a radical resection. Most patients 33 (89.2%) had an advanced tumor stage at the time of diagnosis (17 patients 45.9% stage III and 16 patients 43.2% stage IV), 34 (94.5%) patients showed a tumor depth of >T3, lymph node involvement occurred in 26 patients (70.3%), patients had a high incidence of peritoneal metastasis (16 patients 43.2% at presentation, 30 patients 81.1% at presentation and recurrence) and a low incidence of liver metastases (1 patients 2.7% at presentation, 5 patients 13.5% at presentation and recurrence). The 5-year survival rate after the initial surgery was 10.8%, the mean survival time of 37 patients was 27.1 ± 3.3 months, the mean survival time of patients in stage II, III, and IV were 47.0 ± 12.8 months, 37.1 ± 3.9 months, and 10.5 ± 1.4 months, respectively (P < .000). Colorectal signet-ring cell carcinoma is a rare neoplasm with a predominance in men. Its characteristic features were the advanced stage at the time of diagnosis, a high incidence of peritoneal metastases, a low incidence of liver metastasis, and a poor prognosis.
