STUB1 exacerbates calcium oxalate-induced kidney injury by modulating reactive oxygen species-mediated cellular autophagy via regulating CFTR ubiquitination.

The formation of calcium oxalate (CaOx) crystals in the kidneys leads to renal epithelial damage and the progression of crystalline nephropathy. This study investigated the role of STIP1 homology and U-box protein 1 (STUB1), an E3 ubiquitin ligase, and cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel, in CaOx-related renal damage and autophagy regulation. HK-2 cells were treated with various doses of CaOx monohydrate (COM) to simulate kidney injury in vitro. Cell viability, reactive oxygen species (ROS) production, and apoptosis were assessed. The regulation of CFTR ubiquitination by STUB1 was confirmed by immunoprecipitation. An in vivo model was established by injecting mice with glyoxylate. COM treatment dose-dependently decreased cell viability, increased TNF-α and ROS production, and induced apoptotic cell death in HK-2 cells. COM-treated cells also showed decreased CFTR protein expression. CFTR overexpression improved cell viability and reduced ROS production in COM-stimulated HK-2 cells. Bioinformatics analysis predicted CFTR's ubiquitination binding site for STUB1. Further analysis confirmed the role of STUB1 as a ubiquitin ligase in CFTR degradation. Knockdown of STUB1 upregulated CFTR expression, while STUB1 overexpression had the opposite effect. Knockdown of CFTR reversed the impact of STUB1 deficiency on autophagy. The in vivo experiments showed that CFTR overexpression attenuated kidney tissue damage and CaOx deposition in mice. STUB1-mediated CFTR ubiquitination plays a crucial role in mitigating calcium oxalate-related renal damage by regulating autophagy. Targeting the STUB1/CFTR axis may hold therapeutic potential for treating kidney injury associated with calcium oxalate deposition.

Multivitamins co-intake can reduce the prevalence of kidney stones: a large-scale cross-sectional study.

BACKGROUND: This research aimed to explore the association between changes in the intake of common individual vitamins and combinations of vitamins and the prevalence of kidney calculi. METHODS: We used data from NHANES to investigate the association between nine common vitamins and kidney stone prevalence. Participants were clustered into several vitamin exposure patterns using an unsupervised K-means clustering method. We used logistic regression models and restrictive cubic spline curves to explore the influence of vitamins. RESULTS: The regression model exposed that compared to lower intake, high intake of vitamin B6 [Q4: OR (95% CI) = 0.76 (0.62, 0.93)], vitamin C [Q4: OR (95% CI) = 0.73 (0.59, 0.90)] and vitamin D [Q4: OR (95% CI) = 0.77 (0.64, 0.94)] individually exerted protective effects against the prevalence of kidney stones. Furthermore, the restrictive cubic spline analysis showed that the protective effect against the prevalence of kidney stones is enhanced as the take of vitamin B6 and vitamin D increased. Moreover, with the increase in vitamin C intake, its protective effect may turn into a risk factor. Regarding mixed exposure, Cluster 4 exhibited a significant protective effect against kidney stones compared with Cluster 1 [Model 3: OR (95% CI) = 0.79 (0.64, 0.98)]. CONCLUSIONS: Our research revealed that high levels of vitamin B6 and vitamin D intake were linked to a lower prevalence of kidney stone. With the gradual increase intake of vitamin C, the prevalence of kidney calculi decreased first and then increased. In addition, the co-exposure of nine vitamins is a protective factor for kidney stone disease.

m6A-modified circABCC4 promotes stemness and metastasis of prostate cancer by recruiting IGF2BP2 to increase stability of CCAR1.

Prostate cancer (PCa) is a malignant tumor of the urinary system. CircABCC4 has been demonstrated to promote the development of PCa; however, its regulatory mechanisms in PCa progression remain largely unknown. We found that circABCC4 was highly expressed in PCa tissues and cells, and elevated circABCC4 level indicated a poor overall survival of PCa patients. METTL3 overexpression increased circABCC4 expression via m6A modification in PCa cells. Functionally, knockdown of circABCC4 or METTL3 repressed PCa cell stemness, migration, and invasion in vitro and delayed PCa cancer growth and metastasis in vivo. circABCC4 knockdown-mediated inhibition in PCa cell stemness and metastasis could be counteracted by overexpression of wild-type circABCC4 with m6A sites. Mechanistically, circABCC4 recruited IGF2BP2 protein to CCAR1 mRNA, thereby enhancing CCAR1 mRNA stability and subsequent activation of the Wnt/ß-catenin pathway. Overexpression of CCAR1 counteracted the inhibitory effect of circABCC4 silencing on PCa cell stemness and metastasis. These results revealed that m6A-modified circABCC4 by METTL3 facilitated PCa cell stemness and metastasis by interacting with IGF2BP2 to increase the stability and expression of CCAR and subsequent expression of Wnt/ß-catenin target genes. Our findings suggest circABCC4 as a promising therapeutic target for PCa.

Euchromatic histone lysine methyltransferase 2 facilitates radioresistance in prostate cancer by repressing endoplasmic reticulum protein 29 transcription.

Prostate cancer is one of the most common cancers in men. This study was conducted to investigate the role of euchromatic histone lysine methyltransferase 2 (EHMT2) and endoplasmic reticulum protein 29 (ERP29) in the progression of radioresistance in prostate cancer. The expression of EHMT2 and ERP29 in prostate cancer cells and during the progression of radioresistance was detected using quantitative reverse transcription-polymerase chain reaction and western blotting, and the interaction between EHMT2 and ERP29 was investigated. The proliferation of transfected cells under x-ray irradiation was determined using the methyl thiazolyl tetrazolium and colony formation assays. Flow cytometry was used to analyze the apoptosis of the transfected cells under x-ray irradiation. Nude mice were subcutaneously injected with prostate cancer (DU145) cells stably transfected with sh-ERP29 or sh-NC. The effect of ERP29 expression on radioresistance in nude mice was assessed by x-ray irradiation. The expression of EHMT2 was upregulated and that of ERP29 was downregulated in prostate cancer cells during radioresistance progression. EHMT2 downregulation suppressed radioresistance in DU145 and androgen-sensitive prostate cancer (LNCaP) cells. In irradiated DU145 cells, EHMT2 inhibition decreased the number of colonies and accelerated apoptosis. The transcription of ERP29 was suppressed by EHMT2 by upregulating H3K9me2 and downregulating H3K4me3, thereby regulating radioresistance in prostate cancer cells. In addition, the downregulation of ERP29 promoted the progression of radioresistance in prostate cancer cells in nude mice. EHMT2 promotes radioresistance in prostate cancer cells by repressing ERP29 transcription.

Crosstalk of renal cell carcinoma cells and tumor-associated macrophages aggravates tumor progression by modulating muscleblind-like protein 2/B-cell lymphoma 2/beclin 1-mediated autophagy.

BACKGROUND AIMS: M2-polarized tumor-associated macrophages contribute to the development of multiple human cancers, including renal cell carcinoma (RCC). However, the crosstalk mechanism between M2 macrophages and RCC remains unclear. METHODS: The authors constructed a co-culture system of M2 macrophages differentiated from THP-1 and RCC cells. Microscopic examination and quantitative real­time polymerase chain reaction (qRT-PCR) validated the morphology and types of macrophages. The proliferation, migration and invasion of RCC cells were assessed by Cell Counting Kit 8 (Dojindo Molecular Technologies, Inc, Santa Clara, CA, USA) and Transwell assay (Corning, Corning, NY, USA). Messenger RNA (mRNA) and protein expression of target molecules was detected by qRT­PCR and western blotting. Expression of Ki-67, E-cadherin and N-cadherin was measured by immunofluorescence staining or immunohistochemistry. Molecular interaction was evaluated by RNA pull-down, RNA immunoprecipitation and co-immunoprecipitation. A xenograft model was established to determine tumor growth in vivo. RESULTS: RCC cells triggered the activation of M2 macrophages. Functionally, M2-polarized macrophages facilitated the growth, migration, invasion and epithelial-mesenchymal transition of RCC cells by suppressing autophagy, whereas rapamycin, an activator of autophagy, significantly counteracted the tumor-promoting effects of M2 macrophages. Mechanistically, M2 macrophage-derived C-C motif chemokine 2 (CCL2) enhanced modulation of muscleblind-like protein 2 (MBNL2) expression. MBNL2 raised the stability of B-cell lymphoma 2 (Bcl-2) by directly binding to Bcl-2 mRNA, which endowed RCC cells with malignant properties via inhibition of beclin 1-dependent autophagy. CONCLUSIONS: RCC-induced M2-polarized macrophages secrete CCL2 to promote the growth and metastasis of RCC cells via inhibition of MBNL2/Bcl-2/beclin 1-mediated autophagy, which provide a novel perspective for the development of a therapeutic strategy for -RCC.

The Role of NMP22 and CSTB Levels in Predicting Postoperative Recurrence of Bladder Cancer.

Objective: To investigate the value of preoperative urinary nuclear matrix protein 22 (NMP22) and Cystatin B (CSTB) expressions in evaluating the postoperative recurrence of bladder cancer. Methods: The clinical case data of 102 patients with bladder cancer who underwent surgical treatment from January 2017 to January 2022 were collected, and the patients were divided into a recurrence group (n = 54) and nonrecurrence group (n = 48) according to whether the patients recurred after surgery, and the preoperative NMP22 and CSTB expression levels between the two groups were compared. Receiver operating curve (ROC) was used to analyze the evaluation value of preoperative NMP22 and CSTB expression in patients with bladder cancer postoperative recurrence. Logistic multivariate regression method was used to analyze the correlation between preoperative NMP22 and CSTB expression and postoperative bladder cancer recurrence. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of NMP22 and CSTB single detection and combined detection were evaluated for postoperative recurrence of bladder cancer. Results: The preoperative expression levels of NMP22 and CSTB in the recurrence group were significantly higher than those in the nonrecurrence group (P < 0.05). The results of ROC curve analysis showed that the AUC of preoperative NMP22 and CSTB expression levels to assess postoperative recurrence of bladder cancer was 0.696 and 0.659, respectively (P < 0.05). Logistic multivariate regression analysis showed that preoperative NMP22 and CSTB overexpression was an independent risk factor for postoperative recurrence of bladder cancer (OR = 1.042, 2.307, P < 0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of preoperative NMP22 combined with CSTB in evaluating bladder cancer recurrence after surgery were higher than those of preoperative NMP22 and CSTB alone, and the differences were statistically significant (P < 0.05). Conclusion: Preoperative NMP22 and CSTB conveying is hardly interrelated to postoperative recurrence of bladder carcinoma and has certain appraisal worth for postoperative recurrence of bladder carcinoma, and the combined testing of the two has a taller appraisal worth. NMP22 combined with CSTB detection will help to detect postoperative recurrence of bladder cancer and formulate effective treatment measures in time.

p300/CBP inhibition enhances the efficacy of programmed death-ligand 1 blockade treatment in prostate cancer.

Blockade of programmed death-ligand 1 (PD-L1) by therapeutic antibodies has shown to be a promising strategy in cancer therapy, yet clinical response in many types of cancer, including prostate cancer (PCa), is limited. Tumor cells secrete PD-L1 through exosomes or splice variants, which has been described as a new mechanism for the resistance to PD-L1 blockade therapy in multiple cancers, including PCa. This suggests that cutting off the secretion or expression of PD-L1 might improve the response rate of PD-L1 blockade therapy in PCa treatment. Here we report that p300/CBP inhibition by a small molecule p300/CBP inhibitor dramatically enhanced the efficacy of PD-L1 blockade treatment in a syngeneic model of PCa by blocking both the intrinsic and IFN-γ-induced PD-L1 expression. Mechanistically, p300/CBP could be recruited to the promoter of CD274 (encoding PD-L1) by the transcription factor IRF-1, which induced the acetylation of Histone H3 at CD274 promoter followed by the transcription of CD274. A485, a p300/CBP inhibitor, abrogated this process and cut off the secretion of exosomal PD-L1 by blocking the transcription of CD274, which combined with the anti-PD-L1 antibody to reactivate T cells function for tumor attack. This finding reports a new mechanism of how cancer cells regulate PD-L1 expression through epigenetic factors and provides a novel therapeutic approach to enhance the efficacy of immune checkpoint inhibitors treatment.

Inhibition of noncanonical Wnt pathway overcomes enzalutamide resistance in castration-resistant prostate cancer.

BACKGROUND: Because androgen receptor (AR) signaling is essential for prostate cancer (PCa) initiation and progression, castration is the main approach for treatment. Unfortunately, patients tend to enter a stage called castration-resistant prostate cancer (CRPC) despite the initial response to castration. For various reasons, AR signaling is reactivated in CRPC. As such, AR signaling inhibitors, such as enzalutamide, has been approved by the Food and Drug Administration to treat CRPC in the clinic. However, the limited success of these new drugs suggests an immediate unmet need to understand the underlying mechanisms for resistance so novel targets can be identified to enhance their efficacy. METHODS: An unbiased bioinformatics analysis was performed with the existing human patient dataset and RNA-seq results of in-house PCa cell lines to identify new targets to overcome enzalutamide resistance. Cell viability and growth were detected by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and colony formation assay. Cell invasion and migration were detected by transwell assay. Protein levels were detected by Western blot or immunofluorescence. RESULTS: We found that the noncanonical Wnt signaling was activated in enzalutamide-resistant PCa cells and that the activation of noncanonical Wnt signaling was correlated with AR expression and disease progression. This was validated by the elevated expression of noncanonical Wnt pathway members such as Wnt5a, RhoA, and ROCK in enzalutamide-resistant PCa cells in comparison to their enzalutamide-sensitive counterparts. And, both Y27632, an inhibitor of ROCK, and depletion of ROCK enhanced the efficacy of enzalutamide in enzalutamide-resistant PCa cells. Of significance, a combination of Y27632 and enzalutamide inhibited 22RV1-derived xenograft tumor growth synergistically. Finally, ROCK depletion plus enzalutamide treatment inhibited invasion and migration of enzalutamide-resistant PCa cells via inhibition of epithelial-mesenchymal transition. CONCLUSIONS: The noncanonical Wnt pathway is activated in enzalutamide-resistant PCa and inhibition of noncanonical Wnt pathway overcomes enzalutamide resistance and enhances its efficacy in CRPC.

LINC00511 promotes the malignant phenotype of clear cell renal cell carcinoma by sponging microRNA-625 and thereby increasing cyclin D1 expression.

The expression pattern and detailed roles of long noncoding RNA LINC00511 in clear cell renal cell carcinoma (ccRCC) remain unknown. We measured LINC00511 expression in ccRCC. We clarified the clinical characteristics associated with LINC00511 in ccRCC. We examined the biological roles of LINC00511 in the progression of ccRCC, and we identified the potential mechanisms involved. LINC00511 was upregulated in ccRCC tissues and cell lines. High LINC00511 expression significantly correlated with TNM classification, lymph node metastasis, and short overall survival among patients with ccRCC. Additionally, LINC00511 knockdown restricted ccRCC cell proliferation, colony formation, and metastasis in vitro; accelerated cell cycle arrest at G0-G1 and apoptosis in vitro; and decreased tumor growth in vivo. Investigation of the mechanism revealed that LINC00511 directly interacted with microRNA-625 (miR-625), and the inhibitory effects of the LINC00511 knockdown on malignant characteristics were neutralized by miR-625 silencing. Furthermore, cyclin D1 (CCND1) was identified as a direct target of miR-625 in ccRCC cells. The tumor-suppressive activity of miR-625 upregulation on ccRCC cells was reversed by CCND1 reintroduction. In conclusion, LINC00511 serves as a competing endogenous RNA that regulates CCND1 expression by sponging miR-625 in ccRCC. Hence, the LINC00511/miR-625/CCND1 pathway might be a promising therapeutic target in ccRCC.

Circular RNA circABCC4 as the ceRNA of miR-1182 facilitates prostate cancer progression by promoting FOXP4 expression.

In recent years, circular RNAs (circRNAs) have been identified to be essential regulators of various human cancers. However, knowledge of the functions of circRNAs in prostate cancer remains very limited. The correlation between circABCC4 and human cancer is largely unknown. This study aims to investigate the biological functions of circABCC4 in prostate cancer progression and illustrate the underlying mechanism. We found that circABCC4 was remarkably up-regulated in prostate cancer tissues and cell lines and promoted FOXP4 expression by sponging miR-1182 in prostate cancer cells. CircABCC4 knockdown markedly suppressed prostate cancer cell proliferation, cell-cycle progression, migration and invasion in vitro. Furthermore, silencing of the circRNA also delayed tumor growth in vivo. Taken together, our findings indicated that circABCC4 facilitates the malignant behaviour of prostate cancer by promoting FOXP4 expression through sponging of miR-1182. The circABCC4-miR-1182-FOXP4 regulatory loop may be a promising therapeutic target for prostate cancer intervention.

A case report of primary osteosarcoma originating from kidney.

RATIONALE: Primary osteosarcoma of the kidney is a very rare subtype of renal neoplasms. There are only 27 cases reported in the literature since 1936. In addition, it has a high risk of metastasis and very low survival rate. PATIENT'S CONCERNS: In this report, we present a case of unique large osteosarcoma originated from the left kidney (21 cm × 18 cm × 11 cm) with lung metastasis. A 48-year-old female patient presented with intermittent abdominal distension and gross hematuria. DIAGNOSES: A computed tomography scan of the abdomen confirmed a large solid, partly calcified mass in the left retroperitoneum, with lung metastasis (IV stage according to AJCC). The radical nephrectomy was performed. The postoperation immunohistochemical analysis supporting the diagnosis of osteosarcoma. INTERVENTIONS: The patient received chemotherapy with ifosfamide, cisplatinum, pirarubicin and then target therapy with anlotinib (12 mg per day, per os; days 1-14; 21 days per cycle) after surgery. OUTCOMES: The patient was followed up for 26 months, with no postoperative complications, no tumor recurrence, and no progress in pulmonary metastasis. LESSONS: The case reported here is a unique large osteosarcoma originated from the kidney (21 cm × 18 cm × 11 cm) at an advanced stage (IV). However, the patient's condition was controlled for at least 26 months after surgical resection and postoperative chemotherapy, which had never been reported in the literature before. Additionally, 3 mutated genes were found in the tissue by genetic testing, which we suspect that is the reason why this patient is sensitive to chemotherapy and thus has longer survival.

MLL3 enhances the transcription of PD-L1 and regulates anti-tumor immunity.

Tumor cells utilize the overexpression of the programmed death-1 ligand 1(PD-L1) to escape T-cell controlled immune-surveillance. The clinical therapy that dilapidates PD1 or PD-L1-mediated cancer tolerance has pushed out the need to uncover the molecular regulation of PD-L1 overexpression in the tumor cell. In this study, we identify histone methyltransferase mixed-lineage leukemia protein 3 (MLL3) as a critical regulator of PD-L1 in prostate cancer cells. MLL3 and PD-L1 were highly expressed in the metastatic cancer tissues, compared to the primary cancer tissues. Furthermore, their expressions were highly correlated in the cancer tissues in the databases of TCGA and Xiangya Hospital. We found that MLL3 bound to the enhancer of PD-L1. Depletion of MLL3 decreased the binding level of H3K4me1 in the enhancer of PD-L1 and Pol II Ser-5p in the promoter of PD-L1. Importantly, MLL3 depletion impaired the mouse xenograft growth and decreased the response to PD-L1 antibody treatment in mice. The findings extend the understanding of the biology regulation of PD-L1 transcription and identify the histone writer MLL3 in an important immune checkpoint, and give prominence to a hidden therapeutic target to conquer immune evasion by tumor cells.

Expression of pyruvate kinase M2 in human bladder cancer and its correlation with clinical parameters and prognosis.

BACKGROUND: Pyruvate kinase M2 (PKM2) is a key regulator of the Warburg effect and has critical functions in glycolysis, contributing to the Warburg effect, tumor growth, angiogenesis, cell division, metastasis, and apoptosis. The high expression of PKM2 in various solid tumors renders it a potential biomarker of tumorigenesis and tumor invasion, but the expression and role of PKM2 in bladder cancer have not been studied extensively. PATIENTS AND METHODS: Western blot and immunohistochemistry (IHC) were used to measure the expression of PKM2, and quantitative real-time polymerase chain reaction (PCR) was performed to determine PKM2 mRNA levels. The relationships between PKM2 expression and clinicopathological parameters and prognosis were analyzed using the Kaplan-Meier plots and a Cox proportional hazards regression model. RESULTS: Compared with paired adjacent normal bladder tissues, PKM2 mRNA and protein levels were found to be higher in urothelial carcinoma of the bladder (UCB) samples by real-time PCR and Western blot. By IHC, high expression of PKM2 was seen in 117 of 215 UCBs (54.4%) and in eight of 90 adjacent normal bladder tissues (8.9%). The expression of PKM2 was significantly associated with grade, stage, and lymph node status (P<0.001). In the univariate survival analysis, a significant association between PKM2 expression and shorter patient survival was observed (P<0.001). In different subsets of UCB patients, we found that PKM2 expression was a prognostic factor in patients with G2 (P=0.009), G3 (P<0.001), pTa/pTis (P=0.006), pT1, pT2-4, and pN- disease (P<0.001). Importantly, PKM2 expression (P=0.003), with tumor histological grade (P<0.001), pT (P<0.001), and pN status (P=0.005), was a significant independent prognostic parameter in the multivariate analysis. CONCLUSION: PKM2 protein and mRNA are upregulated in UCBs and may serve as molecular markers for a poor prognosis in patients with UCB.

Overexpression of high mobility group box 1 contributes to progressive clinicopathological features and poor prognosis of human bladder urothelial carcinoma.

BACKGROUND: High mobility group box 1 (HMGB1), a versatile protein with intranuclear and extracellular functions, plays an important role in a variety of human cancers. However, the clinical/prognostic significance of HMGB1 expression in human bladder urothelial carcinoma (BUC) remains unclear. The aim of this study was to investigate the HMGB1 expression in human BUC with regard to its clinical and prognostic significance. PATIENTS AND METHODS: HMGB1 mRNA and protein expressions in tumor and paired normal bladder tissues were detected in 20 BUC cases by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. HMGB1 protein expression in 165 primary BUC tissues was evaluated by immunohistochemistry (IHC), and its correlations with clinicopathological characteristics and prognosis were also analyzed. Student's t-test, χ2 test, Kaplan-Meier plots, and Cox proportional hazard regression model were performed to analyze the data. RESULTS: By using qRT-PCR and Western blot, the upregulated expression of HMGB1 mRNA and protein was detected in BUC, compared with paired normal tissue (P<0.05). By using IHC, high HMGB1 expression was examined in 84 of 165 (51.0%) BUC cases. High HMGB1 expression was significantly correlated with poorer differentiation and higher T and N classification (all P<0.05). Univariate analysis showed that high HMGB1 expression was significantly associated with a shortened patients' overall survival (OS) and disease-free survival (DFS; both P<0.001). In different subgroups of BUC patients, HMGB1 expression was a prognostic factor in patients with different histological grades or T classification (all P<0.05), pN- (both P<0.001) for OS and DFS, and pT1/pN- (P<0.05) for OS. HMGB1 expression, as well as pT and pN status, was an independent prognostic factor for both OS (P=0.001, hazard ratio [HR] =2.973, 95% confidence interval [CI] =1.550-5.704) and DFS (P<0.001, HR =3.019, 95% CI =1.902-4.792) in multivariate analysis. CONCLUSION: Overexpression of HMGB1 may be a new independent molecular marker for the poor prognosis of patients with BUC.

LncRNA XIST/miR-200c regulates the stemness properties and tumourigenicity of human bladder cancer stem cell-like cells.

BACKGROUND: The abnormal expression of non-coding RNAs (ncRNAs), such as microRNAs and long ncRNAs, often contribute to the development of cancers. miR-200c functions as a tumour suppressor that impacts the growth of bladder cancer cells and the epithelial-to-mesenchymal transition (EMT). LncRNA X inactive specific transcript (XIST) is highly expressed in tumour tissues, promotes cancer progression and might act as an miRNA molecular sponge. This study aimed to examine the relationship between lncRNA XIST and miR-200c and to assess their functions in the regulation of the stemness properties and tumourigenicity of human bladder cancer stem cell (BCSC)-like cells. METHODS: Biological effects including cell clone formation, sphere formation, self-renewal properties and mouse tumourigenesis were examined in BCSC-like cells with miR-200c overexpression or XIST knockdown. Real-time PCR and western blotting were used to detect the expression changing of related factors in BCSC-like cells gene models. Dual luciferase reporter assay was used to examine the changes of XIST and miR-200c expression levels. RESULTS: The results indicated that miR-200c overexpression and XIST knockdown could inhibit cell clone formation, self-renewal ability and EMT in BCSC-like cells. miR-200c knockdown could restore the tumour growth inhibition caused by XIST knockdown. CONCLUSION: LncRNA XIST may act as an inhibitor of miR-200c to regulate the stemness properties and tumourigenicity of bladder cancer cells, and our findings might reveal a potential strategy of targeting XIST for bladder cancer therapy.

Oncogenic non-coding RNA NEAT1 promotes the prostate cancer cell growth through the SRC3/IGF1R/AKT pathway.

Steroid receptor co-activator3 (SRC3) has been known to severe as an androgen receptor (AR) coactivator and is involved in the prostate cancer progression. Non-coding RNA (ncRNA) plays an important role in the cancer progression. However, the mechanism underlying the relationship between ncRNA and AR coactivators is still unclear. Here, we found a ncRNA, Nuclear Enriched Abundant Transcript 1 (NEAT1), was able to interact with SRC3 in the prostate cancer cell lines. NEAT1 can upregulate the AKT phosphorylation via a SRC3/IGF1R pathway. In function, NEAT1 promoted the prostate cancer cell growth through IGF1R/AKT signaling pathway. The NEAT1, SRC3, and IGF1R were highly expressed in the patients' samples of prostate cancer. Therefore, we found a novel SRC3 binding ncRNA that can promote the prostate cancer cell growth through SRC3/IGF1R/AKT pathway.