Prostate cancer (PCa) is one of the major men malignancies worldwide. Long noncoding RNAs (lncRNAs) have been reported as essential regulators in human cancers, including PCa. In the present study, lncRNA forkhead box P4 antisense RNA 1 (FOXP4-AS1) was found to be highly expressed in TCGA PCa samples. Upregulation of FOXP4-AS1 was further validated in 64 PCa tissues and predicted poor prognosis in patients with PCa. Functionally, high FOXP4-AS1 level was associated with increased cell proliferation and decreased cell apoptosis, indicating that FOXP4-AS1 exerted oncogenic functions in the tumorigenesis of PCa. Furthermore, FOXP4-AS1 was located in the cytoplasm of PCa cell lines and positively regulated FOXP4. LncRNAs can exert their functions by cooperating with their nearby genes. Mechanistically, FOXP4-AS1 post-transcriptionally regulated FOXP4 by acting as a competing endogenous RNA (ceRNA) in PCa to sponge miR-3184-5p. Considering the upregulation of both FOXP4-AS1 and its nearby gene FOXP4, we further detected the coactivator of FOXP4-AS1 and FOXP4. Mechanism analysis indicated that paired box 5 (PAX5) transcriptionally activated FOXP4-AS1 and FOXP4 in PCa. Collectively, we determined that PAX5-induced upregulation of FOXP4-AS1/FOXP4 axis promoted tumorigenesis of PCa.
Over the past several years, long non‐coding RNAs (lncRNAs) have attracted more and more attention due to their special functions. They are vital biomarkers in multiple diseases. LncRNA HOMEOBOX A11 (HOXA11) has been found to be aberrantly expressed in some kinds of malignant tumors. In this study, we mainly discuss the oncogenic role of it in promoting malignant progression and chemoresistance in lung adenocarcinoma (LUAD) cells. The expression of HOXA11‐AS was much stronger in cisplatin‐resistant LUAD cells. Based on The Cancer Genome Atlas database, patients with high expression of HOXA11‐AS had shorter survival time. Additionally, knockdown of HOXA11‐AS caused positive changes in cell activities of LUAD. For example, cell proliferation and migration were weakened, the epithelial mesenchymal transition process was reversed, and apoptosis was induced. These changes were more obvious in cells treated with cisplatin. Next, the HOXA11‐AS/miR‐454‐3p/Stat3 (signal transducer and activator of transcription 3) pathway was found to influence the cisplatin resistance of LUAD cells. HOXA11‐AS specifically acted as a competing endogenous RNA (ceRNA) in LUAD cells. The combinations among these three genes were demonstrated. Finally, rescue assays were applied to demonstrate the ceRNA pattern consisting of HOXA11‐AS, miR‐454‐3p and Stat3. In conclusion, lncRNA HOXA11‐AS acted as a ceRNA to promote cisplatin resistance of human LUAD cells via the miR‐454‐3p/Stat3 axis.
BackgroundWhether men with a prostate‐specific antigen (PSA) level of 4–10 ng/mL should be recommended for a biopsy is clinically challenging.PurposeTo develop and validate a radiomics model based on multiparametric MRI (mp‐MRI) in patients with PSA levels of 4–10 ng/mL to predict prostate cancer (PCa) preoperatively and reduce unnecessary biopsies.Study TypeRetrospective.SubjectsIn all, 199 patients with PSA levels of 4–10 ng/mL.Field Strength/Sequence3T, T2‐weighted, diffusion‐weighted, and dynamic contrast‐enhanced MRI.AssessmentLesion regions of interest (ROIs) from T2‐weighted, diffusion‐weighted, and dynamic contrast‐enhanced MRI were annotated by two radiologists. A total of 2104 radiomic features were extracted from the ROI of each patient. A random forest classifier was used to build the radiomics model for PCa in the primary cohort. A combined model was constructed using multivariate logistic regression by incorporating the radiomics signature and clinical‐radiological risk factors.Statistical TestsFor continuous variables, variance equality was assessed by Levene's test and Student's t‐test, and Welch's t‐test was used to assess between‐group differences. For categorical variables, Pearson's chi‐square test, Fisher's exact test, or the approximate chi‐square test was used to assess between‐group differences. P < 0.05 was considered statistically significant.ResultsThe combined model incorporating the multi‐imaging fusion model, age, PSA density (PSAD), and the PI‐RADS v2 score yielded area under the curve (AUC) values of 0.956 and 0.933 on the primary (n = 133) and validation (n = 66) cohorts, respectively. Compared with the clinical‐radiological model, the combined model performed better on both the primary and validation cohorts (P < 0.05). Furthermore, the use of the combined model to predict PCa could identify more negative PCa patients than the use of the clinical‐radiological model by 18.4%.Data ConclusionThe combined model was developed and validated to provide potential preoperative prediction of PCa in men with PSA levels of 4–10 ng/mL and might aid in treatment decision‐making and reduce unnecessary biopsies.Level of Evidence: 3Technical Efficacy Stage: 3J. Magn. Reson. Imaging 2020;51:1890–1899.
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