LncRNA SFTA1P mediates positive feedback regulation of the Hippo-YAP/TAZ signaling pathway in non-small cell lung cancer.

Long non-coding RNAs (lncRNAs) regulate numerous biological processes involved in both development and carcinogenesis. Hippo-YAP/TAZ signaling, a critical pathway responsible for organ size control, is often dysregulated in a variety of cancers. However, the nature and function of YAP/TAZ-regulated lncRNAs during tumorigenesis remain largely unexplored. By profiling YAP/TAZ-regulated lncRNAs, we identified SFTA1P as a novel transcriptional target and a positive feedback regulator of YAP/TAZ signaling. Using non-small cell lung cancer (NSCLC) cell lines, we show that SFTA1P is transcriptionally activated by YAP/TAZ in a TEAD-dependent manner. Functionally, knockdown of SFTA1P in NSCLC cell lines inhibited proliferation, induced programmed cell death, and compromised their tumorigenic potential. Mechanistically, SFTA1P knockdown decreased TAZ protein abundance and consequently, the expression of YAP/TAZ transcriptional targets. We provide evidence that this phenomenon could potentially be mediated via its interaction with TAZ mRNA to regulate TAZ translation. Our results reveal SFTA1P as a positive feedback regulator of Hippo-YAP/TAZ signaling, which may serve as the molecular basis for lncRNA-based therapies against YAP/TAZ-driven cancers.

Isolation, characterization and application of a cellulose-degrading strain Neurospora crassa S1 from oil palm empty fruit bunch.

BACKGROUND: Oil palm empty fruit bunch (EFB) is a lignocellulosic waste produced in palm oil industry. EFB mainly consists of cellulose, hemicellulose (mainly xylan) and lignin and has a great potential to be reused. Converting EFB to fermentable sugars and value-added chemicals is a much better choice than treating EFB as waste. RESULTS: A cellulase-producing strain growing on oil palm empty fruit bunch (EFB) was isolated and identified as Neurospora crassa S1, which is able to produce cellulases using EFB as the sole carbon source. The strain started to secret cellulases into the medium after 24 h of cultivation at 30°C and reached its maximal cellulase activity at 240 h. Mass spectroscopy (MS) analysis showed that more than 50 proteins were secreted into the medium when EFB was used as the sole carbon source. Among them, 7 proteins were identified as putative enzymes associated with cellulose degradation. The whole cell culture of Neurospora crassa S1 was used to hydrolyze acid-treated EFB, giving a total sugar yield of 83.2%, which is comparable with that (82.0%) using a well-known cellulase producer Trichoderma reesei RUT-C30 (ATCC56765). CONCLUSION: Neurospora crassa S1 is a commercially promising native cellulase producer for EFB hydrolysis especially when the sugars obtained are to be fermented to products that require use of non-genetically engineered strains.

Efficient production of fermentable sugars from oil palm empty fruit bunch by combined use of acid and whole cell culture-catalyzed hydrolyses.

Empty fruit bunch (EFB) of oil palm trees was converted to fermentable sugars by the combined use of dilute acids and whole fungal cell culture-catalyzed hydrolyses. EFB (5%, w/v) was hydrolyzed in the presence of 0.5% H2 SO4 and 0.2% H3 PO4 at 160 °C for 10 Min. The solid fraction was separated from the acid hydrolysate by filtration and subjected to enzymatic hydrolysis at 50 °C using the whole cell culture of Trichoderma reesei RUT-C30 (2%, w/v), which was prepared by cultivation at 30 °C for 7 days to reach its maximal cellulase activity. The combined hydrolyses of EFB gave a total sugar yield of 82.0%. When used as carbon sources for cultivating Escherichia coli in M9 medium at 37 °C, the combined EFB hydrolysates were shown to be more favorable or at least as good as pure glucose for cell growth in terms of the higher (1.1 times) optical density of E. coli cells. The by-products generated during the acid-catalyzed hydrolysis did not seem to obviously affect cell growth. The combined use of acid and whole cell culture hydrolyses might be a commercially promising method for pretreatment of lignocellulose to get fermentable sugars.