LncRNA LINC00885 promotes bladder cancer progression by targeting the miR-98-5p/PBX3 axis.

Depicted as the most prevalent malignancy, bladder cancer (BLCA) associated deaths in males all around the world. Increasing evidence has uncovered that dysregulation of lncRNA is associated with the complex processes of various tumors. Although recent research concerning bladder cancer has mentioned the participation of lncRNALINC00885, the specific regulatory role of LINC00885 in BLCA hasn't been elucidated. This study aimed to explore the regulatory role of LINC00885 in BLCA. For this purpose, qRT-PCR checked the LINC00885 expression. CCK-8, caspase-3, colony formation, and western blot (WB) experiments were carried out to intestate LINC00885 specific role in BLCA. RIP and RNA pull-down assays were used to study the regulation effect between miR-98-5p and LINC00885 (or PBX3) in BLCA. Results showed that LINC00885 was up-regulated in BLCA and promoted cell proliferation, inhibited cell apoptosis in BLCA. Molecular mechanism experiments displayed that miR-98-5p could bind to LINC00885 and PBX3. Up-regulated miR-98-5p reduced cell proliferation, and facilitated cell apoptosis in BLCA. Besides, miR-98-5p could down-regulated PBX3 expression while LINC0088 could up-regulate PBX3 in BLCA. Final rescue tests demonstrated that PBX3 deficiency reversed the miR-98-5p inhibition effect on the progression of sh-LINC00885#1-transfected cells. In conclusion, LINC00885 enhances BLCA progression by targeting the miR-98-5p/PBX3 axis, revealing that LINC00885 might serve as a novel molecular marker in bladder cancer treatment.

Long noncoding RNA TUG1 decreases bladder cancer chemo-sensitivity toward doxorubicin through elevating KPNA2 expression and activating the PI3K/AKT pathway via adsorbing miR-582-5p.

Long noncoding RNA taurine-upregulated gene1 (TUG1) has been reported to be implicated in the chemo-resistance of bladder cancer. Hence, this study aimed to survey regulatory mechanism by which TUG1 regulates the chemo-resistance of bladder cancer cells to doxorubicin (DOX). Relative expression of TUG1, miR-582-5p, and karyopherin alpha 2 (KPNA2) was detected by qRT-PCR. The viability and proliferation of DOX-resistant bladder cancer cells were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Protein levels were measured by western blot analysis. The apoptosis, migration, and invasion of DOX-resistant bladder cancer cells were determined by flow cytometry or transwell assays. The relationship between TUG1 or KPNA2 and miR-582-5p was verified by dual-luciferase reporter assay. TUG1 and KPNA2 were upregulated while miR-582-5p was downregulated in resistant bladder cancer tissues and cells. TUG1 inhibition elevated cell chemo-sensitivity, facilitated cell apoptosis, and curbed proliferation, migration, invasion, and autophagy of DOX-resistant bladder cancer cells. Also, TUG1 acted as a sponge for miR-582-5p, and miR-582-5p inhibitor reversed TUG1 knockdown-mediated influence on DOX chemo-sensitivity and malignant behaviors in DOX-resistant bladder cancer cells. Furthermore, miR-582-5p targeted KPNA2, and KPNA2 overexpression counteracted the inhibitory impact of miR-582-5p mimic on DOX chemo-resistance and malignant behaviors in DOX-resistant bladder cancer cells. Additionally, TUG1 silencing inactivated the PI3K/AKT pathway through sponging miR-582-5p. TUG1 sponged miR-582-5p to increase KPNA2 expression and activated the KPNA2/PI3K/AKT pathway, thereby elevating DOX chemo-resistance and malignant behaviors in bladder cancer cells.

Hsa_circ_0003221 facilitates the malignant development of bladder cancer cells via resulting in the upregulation of DHCR24 by targeting miR-892b.

PURPOSE: This research concentrated on the biological effects and special mechanism of circ_0003221 in bladder cancer (BLCA). MATERIALS AND METHODS: The level quantification by reverse transcription-quantitative polymerase chain reaction was administrated for circ_0003221, microRNA-892b (miR-892b) and 24-dehydrocholesterol reductase (DHCR24). The biological behaviors were assessed by EDU assay and colony formation assay for proliferation, and transwell assay for cell motility. Glycolytic metabolism was tested using the commercial kits. DHCR24 protein level and cell markers were measured through western blot. The analysis of interaction potential was conducted via dual-luciferase reporter assay and pull-down assay. Circ_0003221 was implemented via tumor xenograft assay in vivo. RESULTS: Abnormal circ_0003221 upregulation was affirmed in BLCA. BLCA cell proliferation, motility and glycolysis were impeded after circ_0003221 level was knocked down. MiR-892b was identified as a target for circ_0003221. Reduction of miR-892b relieved si-circ_0003221-induced anti-tumor response in BLCA cells. In addition, miR-892b targeted DHCR24 and circ_0003221/miR-892b could regulate the level of DHCR24. The effects of si-circ_0003221 were also counteracted by DHCR24 overexpression. CONCLUSIONS: The current evidence elucidated circ_0003221 targeted miR-892b to elevate the DHCR24 level, thus accelerating cell development and glycolytic metabolism of BLCA cells.

Circ_0003146 upregulates SCARB1 expression by acting as a miR-1272 sponge to promote malignant behaviors of clear cell renal cell carcinoma.

Circular RNAs (circRNAs) exhibit essential regulation in the malignant development of clear cell renal cell carcinoma (ccRCC). The aims of this study were to investigate the role and mechanism of circ_0003146 in the biologic behaviors of ccRCC. RNA level analysis was performed through reverse transcription-quantitative PCR assay. Cell proliferation was measured by EdU assay and cell counting kit-8 assay. The protein expression was analyzed using a western blot. Flow cytometry and caspase 3 activity assay were used to assess cell apoptosis. Cell migration and invasion were evaluated via wound healing assay and transwell assay. Circ_0003146 function in vivo was determined by xenograft tumor assay. Dual-luciferase reporter assay was applied for target relation analysis. Circ_0003146 upregulation was detected in ccRCC tissues and cells. Downregulation of circ_0003146 induced inhibition of proliferation, migration, invasion and EMT but the promotion of apoptosis in ccRCC cells. Tumor growth in vivo was inhibited after knockdown of circ_0003146. Circ_0003146 directly interacted with miR-1272, and the miR-1272 sponging effect was responsible for the function of circ_0003146. Scavenger receptor class B type 1 (SCARB1) was a target of miR-1272, and circ_0003146 regulated SCARB1 level by absorbing miR-1272. The regulation of circ_0003146 in ccRCC progression was achieved by upregulating SCARB1 in part. The current findings demonstrated that circ_0003146 contributed to the malignant progression of ccRCC via inducing SCARB1 upregulation by targeting miR-1272.

miR-425-5p suppresses tumorigenesis and DDP resistance in human-prostate cancer by targeting GSK3ß and inactivating the Wnt/ß-catenin signaling pathway.

Prostate cancer (PCa) represents the most frequently diagnosed cancer in men. Cisplatin, also known as cis-diamminedichloroplatinum (DDP), is a standard chemotherapeutic agent used to treat PCa, and DDP resistance remains one important obstacle in DDP-based chemotherapy. In our research, we found miR-425-5p was down-regulated in PCa and even lower in DDP-resistant PCa determined by quantitative polymerase chain reaction; in contrast, GSK3ß mRNA expression was upregulated in PCa and even higher in DDP-resistant PCa. Moreover, there was a modest but significant inverse correlation between the expression of GSK3ß mRNA and miR-425-5p. Functional experiments showed that miR-425-5p mimic inhibited DDP resistance as evidenced by a promoted apoptosis rate (flow cytometry) and suppressed cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay) and expressions of MDR1 andMRP1 (western blotting) in DU145/DDP and PC3/DDP cells. Luciferase reporter assay and RNA immunoprecipitation identifiedGSK3ß was a potential target of miR-425-5p. The effect ofmiR-425-5pmimic on DDP resistance was partially reversed by pcDNA-GSK3ß. Mechanically, miR-425-5p mimic reduced expression of ß-catenin, cyclin D1 and C-myc, which was further blocked when GSK3ß overexpressed. In vivo experiments, recovery of GSK3ß prevented xenograft tumor growth and DDP resistance in the presence of miR-425-5p mimic. To sum up, miR-425-5p upregulation might sensitize human PCa to DDP by targeting GSK3ß and inactivating the Wnt/ß-catenin signaling pathway.