ABSTRACT
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent malignancies worldwide, but there is lack of reliable clinical diagnostic biomarkers. We explored the clinical value and functions of Talin 2 (TLN2) in the progression of ccRCC. METHODS: A bioinformatic analysis was performed to determine the clinical value of TLN2 in ccRCC. TLN2 expression was evaluated by immunohistochemistry (IHC), real-time quantitative polymerase chain reaction (RT-qPCR) and western blot in ccRCC tissues and cells. The functions of TLN2 in ccRCC were investigated by both in vivo and in vitro studies. The functions of TLN2 in ccRCC cell proliferation was determined by CCK-8 assays and colony formation assays. Transwell assays and wound healing assays were performed to detect the effects of TLN2 on ccRCC cell invasion and migration abilities. Apoptosis assay and cell cycle analysis were used to determine the influence of TLN2 on ccRCC cell apoptosis and cell cycle. RESULTS: TLN2 was downregulated in ccRCC tissues and cells. Clinically, TLN2 was confirmed to be an independent factor for ccRCC patient prognosis. Results of colony formation and CCK-8 assays showed that TLN2 overexpression inhibited ccRCC cell growth. Moreover, wound healing assays and transwell assays indicated that TLN2 overexpression inhibited ccRCC cell invasion and migration. In vivo assays also indicated that TLN2 played an important role in ccRCC cell growth and metastasis. TLN2 also inhibited cell cycle progression and promoted apoptosis of ccRCC cells. Mechanistically, TLN2 was confirmed to exert anti-ccRCC functions through Wnt/ß-catenin signaling. CONCLUSIONS: TLN2 served as a tumor regulator of ccRCC via Wnt/ß catenin signaling, suggesting that it could be a promising therapeutic and prognostic biomarker for ccRCC.
ABSTRACT
INTRODUCTION: Ketamine, which is widely used in anesthesia, can induce cortical neurotoxicity in patients. This study aims to investigate the effects of long non-coding RNA LINC00641 on the ketamine-induced neural injury. MATERIALS AND METHODS: In this study, rat pheochromocytoma cells (PC12 cells) were used as a cell model and Sprague-Dawley postnatal day 7 rats were used for experiments in vivo. Ketamine-induced aberrant expression levels of LINC00641, miR-497-5p and brain-derived neurotrophic factor (BDNF) were examined by qRT-PCR. The effects of LINC00641 and miR-497-5p on ketamine-induced neural injury were then examined by MTT assays and TUNEL analysis. In addition, the activity of ROS and caspase-3 was measured. The regulatory relationships between LINC00641 and miR-497-5p, miR-497-5p and BDNF were detected by dual-luciferase reporter assay, respectively. RESULTS: Ketamine induced the apoptosis of PC12 cells, accompanied by down-regulation of LINC00641 and BDNF, and up-regulation of miR-497-5p. LINC00641 overexpression enhanced the resistance to the apoptosis of PC12 cells, while transfection of miR-497-5p had opposite effects. Furthermore, LINC00641 could bind to miR-497-5p and reduce its expression, but indirectly increase the BDNF expression, which was considered as a protective factor in neural injury and activated TrkB/PI3K/Akt pathway. CONCLUSION: Collectively, LINC00641/miR-497-5p/BDNF axis was validated to be an important signaling pathway in modulating ketamine-induced neural injury.
ABSTRACT
This investigation was purposed to extrapolate whether and how lncRNA MALAT1, miR-194-5p, and ACVR2B altered development of clear cell kidney carcinoma (KIRC). We totally gathered 318 pairs of KIRC tissues and adjacent normal tissues, and also purchased human KIRC cell lines and normal human proximal tubular epithelial cell line. Besides, si-MALAT1, pcDNA-MALAT1, miR-194-5p mimic, miR-194-5p inhibitor, and negative control (NC) were, respectively, transfected into KIRC cells. The viability, proliferation, and apoptosis of the cells were determined with CCK-8 assay, colony formation assay, and flow cytometry. Dual-luciferase reporter gene assay was implemented to validate the targeted relationships between MALAT1 and miR-194-5p, as well as between miR-194-5p and ACVR2B. The results showed that highly expressed MALAT1, ACVR2B, and lowly expressed miR-194-5p were associated with larger tumor size (≥4 cm), advanced TNM stage and poor prognosis of KIRC patients, when, respectively, compared with lowly expressed MALAT1, ACVR2B, and highly expressed miR-194-5p (P < 0.05). Transfection of pcDNA-MALAT1, miR-194-5p inhibitor, and pcDNA-ACVR2B conferred the KIRC cells with promoted viability and proliferation, as well as reduced apoptosis (P < 0.05). Treatment of rats with pcDNA-MALAT1, miR-194-5p inhibitor, or pcDNA-ACVR2B also contributed to larger tumor size growing in them (P < 0.05). Moreover, MALAT1 could directly target miR-194-5p to suppress its expression, and ACVR2B was the targeted molecule of miR-194-5p (P < 0.05). Finally, ACVR2B could reverse the effects exerted by miR-194-5p on viability, proliferation, and apoptosis of KIRC cells (P < 0.05). In conclusion, LncRNA MALAT1/miR-194-5p/ACVR2B signaling was regarded as a candidate pathway for modulating KIRC progression.
