GAS1RR, an immune-related enhancer RNA, is related to biochemical recurrence-free survival in prostate cancer.

Prostate cancer (PCa) is one of the malignant tumors of urinary system with a high morbidity. Enhancer RNA is a subclass of long non-coding RNA transcribed from active enhancer regions, which plays a critical role in gene transcriptional regulation. However, the role of enhancer RNA (eRNA) in PCa remains extremely mysterious. This study is aimed at exploring key prognostic eRNAs in PCa. First, we downloaded gene expression data and clinical data of 33 cancer types from UCSC Xena platform. Second, we selected reported putative eRNA-target pairs and performed the Kaplan-Meier survival and correlation analysis to determine the crucial eRNAs most related to biochemical recurrence (BCR)-free survival. Third, we explored the clinical characteristics with the key eRNA GAS1 adjacent regulatory RNA (GAS1RR) and performed a computational difference algorithm and the Cox regression analysis. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore the underlying mechanisms. Finally, we used the pan-cancer data from The Cancer Genome Atlas (TCGA) and performed reverse transcription-quantitative polymerase chain reaction (RT-qPCR) of 18 pairs of specimens to prove the results we acquired. Among all 2695 putative eRNAs, 6 pairs of eRNA-target genes were prominently related to BCR-free survival. Growth arrest-specific protein 1 (GAS1) was a target gene of GAS1RR (r = 0.86, P < 0.001). Patients with low GAS1RR expression were likely to have unfavorable clinical characteristics. The result of computational Cox regression analysis demonstrated that GAS1RR may predict the prognosis of PCa independently. RT-qPCR results illuminated that GAS1RR and GAS1 were both downregulated in PCa tissues, and they show a strong positive correlation. GO and KEGG analyses revealed biological processes that GAS1RR was mainly associated with. Immune infiltration analysis indicated that GAS1RR expression is correlated with the infiltration level of six kinds of immune cells. Our results suggest that GAS1RR may be clinically useful in the prediction of PCa prognosis. Moreover, it may also be a prognostic predictor and theoretic target with great promise in PCa.

Shikonin inhibits the proliferation of cervical cancer cells via FAK/AKT/GSK3ß signalling.

Cervical cancer is one of the most lethal malignancies of the female reproductive system. Shikonin, a naphthoquinone pigment extracted from the traditional medicinal herb, Lithospermum erythrorhizon, has been demonstrated to exert significant inhibitory effects on a variety of tumours in vitro and in vivo. In the present study, the effects of shikonin on cervical cancer and the underlying mechanisms were investigated. The effects of shikonin on the viability on HeLa and SiHa cervical cancer cells was examined using cell counting kit (CCK-8) and colony formation assays. Immunofluorescence assay was performed to detect the levels of the proliferation-related protein, Ki67. Western blot analysis was utilized to measure the phosphorylated and total expression levels of proteins, including focal adhesion kinase (FAK), AKT, and glycogen synthase kinase 3ß (GSK3ß). Cell migration was determined by using wound healing assay. Metastasis-associated 1 (MTA1), TGFß1 and VEGF mRNA expression levels were determined using reverse transcription-quantitative PCR. It was demonstrated that, shikonin inhibited cervical cancer cell proliferation and migration. The data of the present study revealed that shikonin inhibited the proliferation of HeLa and SiHa cells in a concentration- and time-dependent manner. Mechanistically, shikonin blocked the proliferation of cervical cancer cells by downregulating the phosphorylation of FAK, AKT and GSK3ß induced by EGF. In addition, shikonin significantly suppressed cell migration and reduced the expression of migration-related proteins, including MTA1, TGFß1 and VEGF. On the whole, the present study demonstrates that shikonin may exert an inhibitory effect on the cervical cancer cell proliferation and migration through the FAK/AKT/GSK3ß signaling pathway. These findings suggest that shikonin may function as a potential therapeutic drug for the treatment of cervical cancer.