No abstract

No abstract

Cisplatin-induced ototoxicity limits its wide application in the treatment of cancer. A number of pro-inflammatory factors have been shown to be involved in cisplatin-induced ototoxicity. Trichostatin A (TSA) is an anti-inflammatory agent that has been shown to exert protective effects against cisplatin-induced ototoxicity. In the present study, we hypothesized that TSA may protect cochlear hair cells from cisplatin-induced damage by regulating the interleukin (IL)-4/signal transducer and activator of transcription (STAT)6 signaling pathway. Wistar rat cochlear explants were cultured in DMEM. The differentially expressed genes of the basilar membrane were identified by microarray analysis of global expression profiles. Hair cells were stained with rhodamine phalloidin and observed under a scanning electron microscope to evaluate the protective effects of TSA against cisplatin-induced cochlear hair cell damage. The levels of cytokines in the supernatant of the cultured basilar membranes was measured using ELISA. STAT6 and phosphorylated (p-)STAT6 expression was measured by western blot analysis. Morphological observation revealed that cisplatin induced the disarrangement of the cochlear hair cells, as well as the fusion and detachment of the cilia, while these aberrant alterations were inhibited by TSA, suggesting that TSA exerts a protective effect against cisplatin-induced damage to hair cells. Furthermore, the increase in the expression of STAT6 and p-STAT6 induced by cisplatin was reversed by treatment with TSA, accompanied by the decreased expression of IL-1β, IL-4 and IL-6. Therefore, our data demonstrate that TSA reduces cisplatin-induced ototoxicity by inhibiting pro-inflammatory factor-mediated STAT6 signaling. Thus, TSA may be used to prevent the side-effects associated with the use of cisplatin in cancer treatment.

The long non-coding RNA 00858 (LINC00858) has been reported to be an oncogene for various cancer diseases, including osteosarcoma and colorectal cancer. However, the expression pattern and function of LINC00858 in bladder cancer remain largely unknown. The expression level of LINC00858 was measured in tumor tissues and cell lines by RT-qPCR. The role of LINC00858 in bladder cancer cells were studied by gain-and loss-of-function strategies in vitro. Cell proliferation, migration and invasion were assessed by CCK-8, colony formation, wound healing and Transwell chamber assays. At the molecular level, dual luciferase reporter and RNA RIP assays were performed to identify the interaction among LINC00858, microRNA (miR)-3064-5p and cellular communication network factor 2 (CTGF). The results revealed that the expression level of LINC00858 was upregulated in bladder cancer tissues and cell lines including T24, J82 and 5637. Moreover, knockdown of LINC00858 suppressed cell proliferation, migration and invasion in vitro. Mechanistically, LINC00858 functioned as a competitive RNA to increase the expression level of oncogene CTGF by sequestering miR-3064-5p. In conclusion, LINC00858 knockdown inhibited the proliferation, migration and invasion of bladder cancer cells via regulation of the miR-3064-5p/CTGF axis.