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.

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.