Long Noncoding RNA KCNMB2-AS1 Promotes SMAD5 by Targeting miR-3194-3p to Induce Bladder Cancer Progression.

PURPOSE: Bladder cancer is a common malignant tumor of the urinary system, with the fourth-highest incidence of male malignant tumors in Europe and the United States. So far, the mechanism of bladder cancer progression and metastasis has not been clarified. The aim of our study was to validate the way of long noncoding RNA (lncRNA) KCNMB2-AS1 on the metabolism and growth of bladder cancer cells by miR-3194-3p/SMAD5. PATIENTS AND METHODS: The Gene Expression was analyzed by qRT-PCR in bladder cancer tissues and cell lines, with the highly expressed KCNMB2-AS1 screened out. Cell proliferation was detected by Edu staining and clone formation assay, cell migration, and invasion by wound healing and transwell assays. Cell stemness was determined by assessing sphere-forming ability and stemness marker. Correlation between miRNA and lncRNA/gene was verified by dual-luciferase assay and RIP, and the effect of KCNMB2-AS1 on bladder cancer growth by nude mice tumor formation experiment. RESULTS: Here, we revealed the increased level of KCNMB2-AS1 in bladder cancer for the first time. Knockdown of KCNMB2-AS1 in vitro prevented the ability of proliferation, metastasis, and stemness of cancer cells. In vivo, the silencing of KCNMB2-AS1 also prevented tumor growth in vivo. Next, we revealed that KCNMB2-AS1 could interact with miR-3194-3p and uncovered that SAMD5 was a downstream target of miR-3194-3p. CONCLUSION: In conclusion, KCNMB2-AS1 mediated the bladder cancer cells progress by regulating the miR-3194-3p/SAMD5 signal pathway, which would provide a new target for bladder cancer research.

Identification of a novel mutation associated with familial adenomatous polyposis and colorectal cancer.

Colorectal cancer (CRC) is among the most fatal forms of solid tumor in men and women. While the majority of diagnosed CRC cases are sporadic, 15­25% of patients have a family history of adenomatous polyposis and CRC; however, the associated gene mutations remain largely unidentified. The aim of the present study was to investigate the genomes of a four­generational Chinese Han family with familial adenomatous polyposis and CRC to identify the potential genetic anomalies associated with the disease. Diagnoses were made by physical and enteroscopic examinations of all the family members. Mutational analyses of the potential CRC­associated genes were carried out by direct gene sequencing, and the statistically significant differences in polymorphisms between normal and diseased populations were determined. Multiple sequence alignment and protein modeling were conducted using the Vector NTI and DNAMAN software tools. Clinical and pathological features of all the examined patients were consistent with typical familial adenomatous polyposis (FAP) syndrome. From the genomes of these family members, a 131564T>C (p.1125Val>Ala) mutation was identified in exon 15 of the APC gene, and a 1126G>C (p.324Gln>His) mutation was identified in exon 12 of the MUTYH gene. The 131564T>C mutation co­segregated with the affected individuals in the family and was specifically associated with the incidence of CRC (P=0.018<0.05). The 1125Val residue was highly conserved in the APC protein, and the p.1125Val>Ala mutation led to changes in the secondary structure and hydrophilicity of the APC protein. In conclusion, the APC gene mutation 131564T>C is associated with FAP and the pathogenesis of CRC.