No abstract

In a variety of cancers, long non-coding RNAs (lncRNAs) were believed to play important roles. Nevertheless, H19's possible molecular mechanism related to miR-20b-5p has not yet been explored in endometrial cancer. Differential lncRNAs in endometrial cancer were identified based on microarray analysis (GSE23339). In this research, in the first place, H19 expression was detected to be increased but miR-20b-5p to be decreased in endometrial cancer tissues and cells. Besides, H19 expression displayed a negative relationship to miR-20b-5p expression in endometrial cancer tissues. According to gain-and loss-of-function experiments of H19, like a ceRNA, H19 elevated AXL level and HIF-1α expression so as to stimulate the migration, proliferation and EMT process of endometrial cancer. Additionally, the knockdown of H19 slowed down tumor growth, promoted apoptosis and upregulated miR-20b-5p expression but lowered the expressions of HIF-1α, PCNA and AXL in vivo. Furthermore, H19 was also verified to stimulate the activity of endometrial cancer with AXL inhibitor BGB324 in vitro and in vivo. To sum up, H19 accelerates the tumor formation of endometrial cancer through the miR-20b-5p/AXL/HIF-1α signaling pathway, thereby providing a novel target for diagnosing and treating endometrial cancer.

The tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) has been shown to selectively induce death in cancer cells without affecting healthy cells. Most glioma cells are resistant to TRAIL-induced apoptosis. Resistance to TRAIL limits its potential use as a drug for therapy of glioma. The present study was conducted to identify bioactive compounds that have the potential to sensitize U87 glioblastoma cells to TRAIL. Evodiamine, a major bioactive compound of the Chinese herb Evodiae fructus, has been reported to sensitize U87 glioblastoma cells to TRAIL. TRAIL and evodiamine, in combination or alone, were used to treat U87 glioblastoma cells. We show that evodiamine treatment inhibited cell growth in a dose-dependent manner; however, TRAIL alone failed to exert any cytotoxic effect. Combining TRAIL with evodiamine significantly increased the apoptotic rate of U87 glioblastoma cells, as compared to evodiamine treatment alone. Further investigation of the mechanism underlying these effects revealed that the evodiamine + TRAIL effect is associated with the increased expression of death receptor (DR)4, DR5, caspase-8 and cleaved caspase-3. The present study demonstrated, for the first time to the best of our knowledge, that evodiamine can sensitize U87 glioblastoma cells to TRAIL via the death receptor pathway. Thus, our results suggest that combined treatment with evodiamine and TRAIL may represent a novel chemotherapeutic strategy for the therapy of glioma.

Rapamycin is a 31-member ring macrolide produced by Streptomyces hygroscopicus and has many applications in clinical medicine. In the present work, several protoplasts-related techniques including protoplasts mutation, intraspecies and interspecies protoplasts fusion were tried to improve the rapamycin productivity in S. hygroscopicus. Although mutation and fusion of different protoplasts of S. hygroscopicus did not improve the productivity of rapamycin significantly, the interspecies fusion of protoplasts of S. hygroscopicus D7-804 and Streptomyces erythreus ZJU325 could have brought about one high-yield (345 mg/L) rapamycin producer with 23.6% higher than that of the parental strain. Then, with seven mutants of S. hygroscopicus with different features and rapamycin productivities as the parental strains, only one-round genome shuffling has generated a high-yield rapamycin-producing strain with an outstanding yield of 445 mg/L. The systematic research of protoplast-related techniques has established an applicable way to generate high-yield strains from original microorganisms which can only produce low amount of expected natural products, without information of target gene clusters and gene sequences.