Long non-coding RNAs (lncRNAs) have been implicated in various human malignancies, but the molecular mechanism of lncRNA TINCR ubiquitin domain containing (TINCR) in bladder cancer remains unclear. The present study found that the expression of TINCR was significantly increased in bladder cancer tissues and cell lines, when compared with that in adjacent normal tissues and normal urinary tract epithelial cell line SV-HUC-1, respectively. Moreover, the high expression of TINCR was associated with tumor metastasis and advanced tumor, node, metastasis stage, as well as reduced overall survival rates of patients with bladder cancer. Further investigation revealed that microRNA (miR)-7 was negatively mediated by TINCR in bladder cancer cells. Silencing of TINCR expression significantly increased miR-7 expression and reduced bladder cancer cell proliferation, migration and invasion, while knockdown of miR-7 expression reversed the inhibitory effects of TINCR downregulation on bladder cancer cells. mTOR was then identified as a target gene of miR-7 in bladder cancer, and it was demonstrated that overexpression of mTOR reversed the inhibitory effects of miR-7 on bladder cancer cells. In conclusion, this study suggests that TINCR/miR-7/mTOR signaling may be a potential therapeutic target for bladder cancer.

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Background The systemic immune-inflammation index (SII) has recently emerged as a predictor of survival in non-small cell lung cancer patients. There is also tight correlation between radiotherapy and immune status, and brain metastases (BM) radiotherapy is an important treatment in patients with BM from lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations. Hence, this study aimed to present the prognostic value of SII and its dynamic changes during BM radiotherapy in EGFR-mutant lung adenocarcinoma patients with BM. Methods Patients with EGFR-mutant lung adenocarcinoma who received BM radiotherapy between November 2011 and April 2021 were included in this retrospective study. The SII was calculated using data acquired within 1 week before the start of radiation treatment and 1 week before its completion. According to the cutoff value of SII before radiation treatment determined using receiver operating characteristic curve analyses, we divided the patients into a high group and a low group. Patients were further classified into high–high, high–low, low–low, and low–high groups based on dynamic changes in SII. Prognostic values of the SII and other factors were determined using the Kaplan–Meier method, as well as univariate and multivariate Cox analysis. Results A total of 202 patients met the inclusion criteria, and the median overall survival (OS) of the entire cohort was 36 months. According to the SII cutoff of 859.79, an SII value below this cutoff was associated with longer OS (hazard ratio 0.6653, 95% confidence interval 0.4708–0.9402, P < 0.05). The patients in the low–low group, whose SII within 1 week before the start and end of BM radiotherapy were below the cutoff, had a median OS of 55.2 months, which was significantly longer than the OS in all other groups (P < 0.05). Univariate and multivariate analyses confirmed that dynamic SII change (P = 0.032), Lung-molGPA (P < 0.001), and thoracic radiation (P = 0.048) were independently correlated with OS. Conclusions The SII and its dynamic change may have a prognostic value in patients with EGFR-mutant lung adenocarcinoma treated with BM radiotherapy.

Background Breast cancer is the most common cancer in women worldwide. More than 70% of breast cancers are estrogen receptor (ER) alpha positive. Compared with ER alpha-negative breast cancer, which is more aggressive and has a shorter survival time, ER alpha-positive breast cancer could benefit from endocrine therapy. Selective estrogen receptor modulators, such as tamoxifen, are widely used in endocrine therapy. Approximately half of ER alpha-positive breast cancer patients will eventually develop endocrine resistance, making it a major clinical challenge in therapy. Thus, decoding the throughput of estrogen signaling, including the control of ER alpha expression and stability, is critical for the improvement of breast cancer therapeutics. Methods TRIM3 and ER alpha protein expression levels were measured by western blotting, while the mRNA levels of ER alpha target genes were measured by RT–PCR. A CCK-8 assay was used to measure cell viability. RNA sequencing data were analyzed by Ingenuity Pathway Analysis. Identification of ER alpha signaling activity was accomplished with luciferase assays, RT–PCR and western blotting. Protein stability assays and ubiquitin assays were used to detect ER alpha protein degradation. Ubiquitin-based immunoprecipitation assays were used to detect the specific ubiquitination modification on the ER alpha protein. Results In our current study, we found that TRIM3, an E3 ligase, can promote ER alpha signaling activity and breast cancer progression. TRIM3 depletion inhibits breast cancer cell proliferation and migration, while unbiased RNA sequencing data indicated that TRIM3 is required for the activity of estrogen signaling on the -genome-wide scale. The immunoprecipitation assays indicated that TRIM3 associates with ER alpha and promotes its stability, possibly by inducing K63-linked polyubiquitination of ER alpha. In conclusion, our data implicate a nongenomic mechanism by which TRIM3 stabilizes the ER alpha protein to control ER alpha target gene expression linked to breast cancer progression. Conclusion Our study provides a novel posttranslational mechanism in estrogen signaling. Modulation of TRIM3 expression or function could be an interesting approach for breast cancer treatment. Graphical abstract

Background and PurposeEpidermal growth factor receptor (EGFR)-mutant lung cancers are associated with a high risk of developing brain metastases (BM). Craniocerebral radiotherapy is a cornerstone for the treatment of BM, and EGFR-TKIs act on craniocerebral metastases”. However, whether EGFR-TKIs combined with craniocerebral radiotherapy can further increase the efficacy and improve the prognosis of patients is unclear. This study aimed to evaluate the difference in efficacy between targeted-therapy alone and targeted-therapy combined with radiotherapy in EGFR-mutant lung adenocarcinoma patients with BM.Materials and MethodsA total of 291 patients with advanced non-small cell lung cancer (NSCLC) and EGFR mutations were enrolled in this retrospective cohort study. Propensity score matching (PSM) was conducted using a nearest-neighbor algorithm (1:1) to adjust for demographic and clinical covariates. Patients were divided into two groups: EGFR-TKIs alone and EGFR-TKIs combined with craniocerebral radiotherapy. Intracranial progression-free survival (iPFS) and overall survival (OS) were calculated. Kaplan–Meier analysis was used to compare iPFS and OS between the two groups. Brain radiotherapy included WBRT, local radiotherapy, and WBRT+Boost.ResultsThe median age at diagnosis was 54 years (range: 28–81 years). Most patients were female (55.9%) and non-smokers (75.5%). Fifty-one pairs of patients were matched using PSM. The median iPFS for EGFR-TKIs alone (n=37) and EGFR-TKIs+craniocerebral radiotherapy (n=24) was 8.9 and 14.7 months, respectively. The median OS for EGFR-TKIs alone (n=52) and EGFR-TKIs+craniocerebral radiotherapy (n=52) was 32.1 and 45.3 months, respectively.ConclusionIn EGFR-mutant lung adenocarcinoma patients with BM, targeted therapy combined with craniocerebral radiotherapy is an optimal treatment.