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Long non-coding RNAs (lncRNAs) are involved in the pathogenesis of prostate cancer (PCa) as competitive endogenous RNA. The present study aimed to investigate the molecular mech anisms of lncRNA small nucleolar RNA host gene 16 (SNHG16) in the proliferation and metastasis of PCa cells. Cancer tissues and adjacent normal tissues were collected from 80 patients with PCa who did not receive any treatment. Reverse transcription-quantitative PCR analysis was performed to detect the expression levels of SNHG16, hsa-microRNA (miRNA/miR)-373-3p and transforming growth factor-β receptor type 2 (TGF-β-R2), and Spearman's correlation coefficient analysis was performed to assess the correlations between these molecules. Furthermore, the effects of SNHG16 knockdown and overexpression on the biological functions of DU-145 PCa cells and TGF-β-R2/SMAD signaling were analyzed. The dual-luciferase reporter assay was performed to assess the associations between SNHG16 and miR-373-3p, and TGF-β-R2 and miR-373-3p, the effects of which were verified via rescue experiments. The results demonstrated that the expression levels of SNHG16 and TGF-β-R2 were significantly upregulated in PCa tissues, whereas miR-373-3p expression was significantly downregulated (P<0.001). In addition, negative correlations were observed between SNHG16 and miR-373-3p (rho, -0.631) and miR-373-3p and TGF-β-R2 (rho, -0.516). Overexpression of SNHG16 significantly promoted the proliferation, migration and invasion of PCa cells (P<0.05), and significantly increased the protein expression levels of TGF-β-R2, phosphorylated (p)-SMAD2, p-SMAD3, c-Myc and E2F4 (P<0.001). Notably, the results revealed that miR-373-3p is a target of SNHG16, and miR-373-3p knockdown rescued short hairpin (sh)-SNHG16-suppressed cellular functions by promoting TGF-β-R2/SMAD signaling. The results also revealed that miR-373-3p targets TGF-β-R2. Notably, transfection with miR-373-3p inhibitor rescued sh-TGF-β-R2-suppressed cell proliferation and migration. Taken together, the results of the present study suggest that SNHG16 promotes the proliferation and migration of PCa cells by targeting the miR-373-3p/TGF-β-R2/SMAD axis.

PurposeThe most common disadvantage of 11C-choline positron emission tomography and computed tomography (PET/CT) in diagnosing early-stage prostate cancer (PCa) is its poor sensitivity. In spite of many efforts, this imaging modality lacks the ideal parameter of choline metabolism for the diagnosis of PCa, and the single metabolic parameter, that is, maximal standardized uptake value (SUVmax), based on this imaging modality is insufficient. 11C-choline PET/CT-based multi-metabolic parameter combination can help break this limitation.Materials and MethodsBefore surgery, SUVmax of choline, which is the most common metabolic parameter of 11C-choline PET/CT, mean standardized uptake value (SUVmean), prostate-to-muscle (P/M) ratio, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from 74 patients with histologically proven PCa were quantified. A total of 13 patients with focal chronic prostatitis without severe features and 30 patients with benign prostate hyperplasia were used for comparison. Univariable and multivariable analyses were performed to compare the patient characteristics and metabolic parameters of 11C-choline PET/CT. The performance of single parameters and the combination of parameters were assessed by using logistic regression models.ResultsThe comparable c-statistics, which mean the area under the ROC curve in the logistic regression model, of SUVmax, SUVmean, and P/M ratio are 0.657, 0.667, and 0.672, respectively. The c-statistic significantly rose to 0.793 when SUVmax and SUVmean were combined with the P/M ratio. This parameter combination performed the best for PCa cases with all biochemical recurrence risks and for PCa patients grouped by different risk. The greatest improvement over a single parameter, such as P/M ratio, was noted in the group of low-risk PCa, with values of 0.535 to 0.772 for the three-parameter combination. And in the histopathological level, the Ki-67 index is positively correlated with the P/M ratio (r=0.491, p=0.002).ConclusionP/M ratio is a more ideal parameter than SUVmax as a single parameter in early-stage PCa diagnosis. According to our data, the combination of SUVmax, SUVmean, and P/M ratio as a composite parameter for diagnosis of early stage PCa improves the diagnostic accuracy of 11C-choline PET/CT.

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