Background: Long non-coding RNAs (lncRNAs) function as a class of significant mediators in prostate cancer (PCa), and this study mainly discussed the molecular mechanism of lncRNA growth arrest-specific 5 (GAS5) in PCa progression and radiosensitivity. Materials and Methods: GAS5 and microRNA-320a (miR-320a) levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and migration were severally examined through 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) and transwell assays. PCa cells were treated with X-ray irradiation. Cell survival and apoptosis rate were assayed using colony formation assay and flow cytometry, respectively. The apoptosis-related protein and Rab GTPase 21 (RAB21) protein levels were measured by Western blot. The relation between miR-320a and GAS5 or RAB21 was assessed via the dual-luciferase reporter assay. The effect of GAS5 on radiosensitivity of PCa in vivo was evaluated by xenotransplantation assay. Results: GAS5 was down-regulated in PCa tissues and cells. GAS5 overexpression suppressed cell viability and migration while facilitated radiosensitivity of PCa cells. GAS5 was a molecular sponge of miR-320a. The effects of GAS5 up-regulation on PCa cells were accomplished by sponging miR-320a. MiR-320a targeted RAB21 and GAS5 up-regulated RAB21 expression via targeting miR-320a. RAB21 knockdown reversed the effects of miR-320a inhibition on PCa cells. GAS5 promoted the radiosensitivity of PCa by the miR-320a/RAB21 axis in vivo. Conclusion: Collectively, GAS5 restrained tumor development and expedited the radiosensitivity in PCa by the miR-320a/RAB21 axis, which provided a molecular regulatory mechanism of GAS5/miR-320a/RAB21 in PCa development and radioresistance.
Background: Renal cell carcinoma (RCC) is the predominant type of malignant tumor in kidney cancer. Finding effective biomarkers, particularly those based on the tumor immune microenvironments (TIME), is critical for the prognosis and diagnosis of RCC. Increasing evidence has revealed that long non-coding RNAs (lncRNAs) play a crucial role in cancer immunity. However, the comprehensive landscape of immune infiltration-associated lncRNAs and their potential roles in the prognosis and diagnosis of RCC remain largely unexplored.Methods: Based on transcriptomic data of 261 RCC samples, novel lncRNAs were identified using a custom pipeline. RCC patients were classified into different immune groups using unsupervised clustering algorithms. Immune-related lncRNAs were obtained according to the immune status of RCC. Competing endogenous RNAs (ceRNA) regulation network was constructed to reveal their functions. Expression patterns and several tools such as miRanda, RNAhybrid, miRWalk were used to define lncRNAs-miRNAs-mRNAs interactions. Univariate Cox, LASSO, and multivariate Cox regression analyses were performed on the training set to construct a tumorigenesis-immune-infiltration-related (TIR)-lncRNA signature for predicting the prognosis of RCC. Independent datasets involving 531 RCC samples were used to validate the TIR-lncRNA signature.Results: Tens of thousands of novel lncRNAs were identified in RCC samples. Comparing tumors with controls, 1,400 tumorigenesis-related (TR)-lncRNAs, 1269 TR-mRNAs, and 192 TR-miRNAs were obtained. Based on the infiltration of immune cells, RCC patients were classified into three immune clusters. By comparing immune-high with immune-low groups, 241 TIR-lncRNAs were identified, many of which were detected in urinary samples. Based on lncRNA-miRNA-mRNA interactions, we constructed a ceRNA network, which included 25 TR-miRNAs, 28 TIR-lncRNAs, and 66 TIR-mRNAs. Three TIR lncRNAs were identified as a prognostic signature for RCC. RCC patients in the high-risk group exhibited worse OS than those in the low-risk group in the training and testing sets (p < 0.01). The AUC was 0.9 in the training set. Univariate and multivariate Cox analyses confirmed that the TIR-lncRNA signature was an independent prognostic factor in the training and testing sets.Conclusion: Based on the constructed immune-related lncRNA landscape, 241 TIR-lncRNAs were functionally characterized, three of which were identified as a novel TIR-lncRNA signature for predicting the prognosis of RCC.
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