Identification of an Immune-Related LncRNA Prognostic Signature in Uterine Corpus Endometrial Carcinoma Patients.

BACKGROUND: Uterine corpus endometrial carcinoma (UCEC) is the third most prevalent female reproductive system malignant tumor with poor prognosis, particularly at advanced stage. On the other hand, recent studies have reported the prognostic role of long non-coding RNAs (lncRNAs) in UCEC. The aim of this study was to determine the immune-related lncRNA signature for predicting overall survival (OS) in UCEC patients. METHODS: The genomic data and clinical information of UCEC patients were extracted from the Cancer Genome Atlas. Pearson's correlation analysis was carried out to identify the immune-related lncRNAs. Univariate and multivariate Cox regression analyses were conducted to obtain the prognostic lncRNAs from the immune-related lncRNAs for the construction of the prognostic signature. Afterwards, the UCEC patients were divided into high-risk and low-risk groups. The prognostic value of the signature was assessed by survival, receiver operating characteristic (ROC), and nomogram analyses. Finally, the immune status for high-risk and low-risk groups was evaluated by the ESTIMATE algorithm. RESULTS: A total of 13 immune-related lncRNAs (AC108860.2, AC015849.5, AL592494.3, LINC01234, U91319.1, AC092969.1, AL356133.2, AC103563.2, AL138962.1, AC138965.1, LINC01687, AC091987.1, and MIR7-3HG) were finally identified for the construction of the prognostic signature. Patients in the high-risk group had worse prognosis than those in the low-risk group. The prognostic signature was confirmed as an independent prognostic factor through the multivariate Cox regression analysis. The nomogram based on the prognostic signature and clinicopathologic features was constructed with a superior overall predictive power to evaluate the survival outcomes in UCEC patients. Finally, according to the ESTIMATE algorithm results, we discovered different immune statuses in the low-risk and high-risk groups. CONCLUSIONS: The immune-related lncRNA signature for the assessment of the OS of UCEC patients had a good practical value.

Prognostic Value of Expression of MicroRNAs in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: microRNAs are widely involved in a variety of life processes and considered as potential biomarkers of tumor prognosis. A growing number of studies have documented that miRNAs were associated with outcome in NSCLC patients and can act as a prognostic marker. However, existing studies concerning the relationship between miRNAs and outcome in NSCLC patients were contentious and dispersive. Therefore, a systematic metaanalysis to explore the prognostic value of miRNAs on NSCLC patients is urgently needed. METHODS: Electronic databases, including PubMed, EMBASE, and Web of Science were searched for all relevant articles. Only articles investigating the survival effect of microRNAs on NSCLC patients were included in this meta-analysis. Hazard ratios (HRs) with 95% confidence interval (CI) were extracted and pooled on overall survival (OS) and progression free survival (PFS)/disease-specific survival (DSS). RESULTS: 28 articles were finally included in the overall meta-analysis. The pooled results revealed that high expression miR-21 (HR = 2.82, 95% CI: 2.10 - 3.79), miR-200c (HR = 2.05, 95% CI: 1.36 - 3.07), and miR-125b (HR = 1.72, 95% CI: 1.30 - 2.28) were negatively associated with survival in NSCLC patients. Conversely, high expression miR-148b (HR = 0.37, 95% CI: 0.19 - 0.70), miR-365 (HR = 0.40, 95% CI: 0.27 - 0.59), miR-124 (HR = 0.29, 95% CI: 0.16 - 0.53), miR-32 (HR = 0.46, 95% CI: 0.33 - 0.65), miR-146a (HR = 0.35, 95% CI: 0.18 - 0.68), and miR-375 (HR = 0.66, 95% CI: 0.45 - 0.96) were significantly associated with better prognosis. Meanwhile, the expression of miR-93 (HR = 1.19, 95% CI: 0.38 - 3.69) and miR-126 (HR = 0.38, 95% CI: 0.12 - 1.16) showed no relationship with NSCLC prognosis. CONCLUSIONS: Our meta-analysis provided the evidence that miR-21, miR-200c, miR-125b, miR-148b, miR-365, miR-124, miR-32, miR-146a, and miR-375 can act as prognostic biomarkers in NSCLC.

miRNA­375 regulates the cell survival and apoptosis of human non­small cell carcinoma by targeting HER2.

micro (mi)­RNAs are a class of small non­coding RNAs that regulate gene expression by binding to the 3'­untranslated region of mRNA, which may lead to mRNA degradation or transcription regulation. Previous studies indicated that miRNAs are important for the pathogenesis of human cancer. miR­375 has been implicated in various tumor types; however, the biological activity in human non­small cell lung carcinoma (NSCLC) cells remains to be fully elucidated. The purpose of the present study was to investigate the biological importance of miR­375 in human NSCLC cells. The expression of miRNAs and mRNA was determined using reverse transcription­quantitative polymerase chain reaction. Cell proliferation was analyzed using a Cell Counting kit­8 assay. Cell apoptosis was analyzed using a fluorescence­activated cell sorting assay. The migration and invasion abilities of cells were evaluated using an in vivo mouse model. Dual­luciferase assay and western blotting were used to determine the potential target of miR­375. The results indicated that the expression of miR­375 in human NSCLC cells was significantly downregulated and induction of miR­375 may inhibit the proliferation of human NSCLC cells by inducing apoptosis. An animal model was used to determine that the upregulation of miR­375 inhibited the migration and invasion of A549 human NSCLC cells in vivo. It was also determined that human epidermal growth factor receptor 2 (HER­2) was a direct target gene of miR­375 and induction of miR­375 may reduce the expression of HER­2 in human NSCLC cells. These findings suggested that miR­375 may act as a potential therapeutic target for human NSCLC cancer in the future.

Histone deacetylase inhibitors regulate P-gp expression in colorectal cancer via transcriptional activation and mRNA stabilization.

Histone deacetylase inhibitors (HDACIs) are emerging as a novel class of anti-tumor drugs. But the effect of HDACIs in tumors treatment has been disappointing, which mainly due to the acquisition of resistance to HDACIs. However, the underlying mechanisms have not been clearly understood. In this study, it was found that HDACIs SAHA and TSA increased P-gp expression in CRC cells, which has been well known to contribute to drug resistant. The mechanisms underlying these effects were investigated. We showed that HDACIs enhanced transcriptional activity of P-gp protein encoding gene ABCB1. HDACIs treatment also increased the protein and mRNA expression of STAT3, but not PXR, CAR, Foxo3a or ß-catenin, which are known to be involved in ABCB transcription regulation. Interestingly, knockdown of STAT3 significantly attenuated HDACIs-induced P-gp up-regulation in colorectal cancer cells, suggesting that STAT3 plays a crucial role in HDACIs-up-regulated P-gp. Furthermore, this study revealed for the first time that HDACIs enhanced the stability of ABCB1 at post-transcriptional level. Taken together, these results proved that HDACIs induced P-gp expression by two distinct ways, transcriptional activation and mRNA stabilization. Our results suggested that more attention should be paid to the cancer treatment using HDACIs since they will induce multidrug resistance in cancer cells.