Therapeutic applications of microRNA (miRNA) in KRAS-driven pancreatic cancers might be valuable, but few studies have explored this area. Here, we report that miR-96 directly targets the KRAS oncogene and functions as a tumor-suppressing miRNA in pancreatic cancer cells. Ectopic expression of miR-96 through a synthetic miRNA precursor inhibited KRAS, dampened Akt signaling, and triggered apoptosis in cells. In human clinical specimens, miR-96 was downregulated or deleted where an association with KRAS elevations was observed. In vitro and in vivo assays established that miR-96 decreased cancer cell invasion and migration and slowed tumor growth in a manner associated with KRAS downregulation. Our findings identify miR-96 as a potent regulator of KRAS, which may provide a novel therapeutic strategy for treatment of pancreatic cancer and other KRAS-driven cancers.
This paper studies electric vehicle charger location problems and analyzes the impact of public charging infrastructure deployment on increasing electric miles traveled, thus promoting battery electric vehicle (BEV) market penetration. An activity-based assessment method is proposed to evaluate BEV feasibility for the heterogeneous traveling population in the real world driving context. Genetic algorithm is applied to find (sub)optimal locations for siting public charging stations. A case study using the GPS-based travel survey data collected in the greater Seattle metropolitan area shows that electric miles and trips could be significantly increased by installing public chargers at popular destinations, with a reasonable infrastructure investment.
Background MicroRNAs act as tumor suppressors or oncogenes. The pathological roles of miRNAs in gastric tumorigenesis are largely unknown. Although miR-10b was identified as an miRNA deregulator expressed in gastric cancer (GC), there also exists some debate on whether miR-10b is acting as tumor suppressor or oncogene in GC. Methods Quantitative RT-PCR was employed to investigate the level of miR-10b in GC tissues and matched adjacent normal tissues (n = 100). In vitro cell proliferation, apoptosis assays, cell migration, and invasion assays were performed to elucidate the biological effects of miR10b. Because silencing of miRNA by promoter CpG island methylation may be an important mechanism in tumorigenesis, GC cells were treated with 5-aza-2 0 -deoxycytidine and trichostatin A, and expression changes of miR-10b were subsequently examined by quantitative RT-PCR. Furthermore, the methylation status of the CpG island upstream of miR-10b was analyzed by methylation-specific PCR in GC tissues (n = 29). Results We showed here that miR-10b was significantly downregulated in GC cell lines and tissues as demonstrated by quantitative real-time PCR. Overexpression of miR-10b in MGC-803 and HGC-27 dramatically suppressed cell proliferation, migration, invasion, and induced apoptosis. Moreover, we demonstrated that T-cell lymphoma invasion and metastasis (Tiam1) was a target of miR-10b. Furthermore, 5-aza-2 0 -deoxycytidine and trichostain A increased miR-10b expression, and the methylation level was high in the CpG islands upstream of miR-10b gene. Conclusions Taken together, these findings suggest that miR-10b may function as a novel tumor suppressor and is partially silenced by DNA hypermethylation in GC.
This paper evaluates the energy consumption and battery performance of city transit electric buses operating on real day-today routes and standardized bus drive cycles, based on a developed framework tool that links bus electrification feasibility with real-world vehicle performance, city transit bus service reliability, battery sizing and charging infrastructure. The impacts of battery capacity combined with regular and ultrafast charging over different routes have been analyzed in terms of the ability to maintain city transit bus service reliability like conventional buses. The results show that ultrafast charging via frequent short-time boost charging events, for example at a designated bus stop after completing each circuit of an assigned route, can play a significant role in reducing the battery size and can eliminate the need for longer duration charging events that would cause schedule delays. The analysis presented shows that significant benefits can be realized by employing multiple battery configurations and flexible battery swapping practices in electric buses. These flexible design and use options will allow electric buses to service routes of varying city driving patterns and can therefore enable meaningful reductions to the cost of the vehicle and battery while ensuring service that is as reliable as conventional buses.
Increasing evidence shows that abnormal microRNAs (miRNAs) expression is involved in tumorigenesis. They might be the novel biomarkers or therapeutic targets in disease treatment. miR-29 family was previously reported to act as tumor suppressors or oncogenes in diverse cancers. However, their accurate expression, function and mechanism in gastric cancer (GC) are not well known. Here, we found that the expression of miR-29 family members was significantly reduced in GC compared with adjacent controls. Among them, miR-29c had the most reduced percentage in GC and was associated with aggressive and progressive phenotypes of GC. We further demonstrated that miR-29 family acted as tumor suppressors through targeting CCND2 and matrix metalloproteinase-2 genes in GC. Moreover, the inverse relationship between miR-29 family and their targets was verified in patients and xenograft mice. Finally, reintroduction of miR-29 family significantly inhibited tumor formation of GC cells in the xenograft mice. Take together, our finding characterized the expression properties of miR-29 family, contributed to the function and molecular mechanism of miR-29 family in GC and implied that miR-29 family might be employed as novel prognostic markers and therapeutic targets of GC.
Rhomboid proteins perform a wide range of important functions in a variety of organisms. Recent studies have revealed that rhomboid proteins are involved in human cancer progression; however, the underlying molecular mechanism remains largely unclear. Here we show that RHBDD1, a rhomboid intramembrane serine protease, is highly expressed and closely associated with survival in patients with colorectal cancer. We observe that inactivation of RHBDD1 decreases tumor cell growth. Further studies show that RHBDD1 interacts with proTGFα and induces the ADAM-independent cleavage and secretion of proTGFα. The secreted TGFα further triggers the activation of the EGFR/Raf/MEK/ERK signalling pathway. Finally, the positive correlation of RHBDD1 expression with the EGFR/Raf/MEK/ERK signalling pathway is further corroborated in a murine model of colitis-associated colorectal cancer. These findings provide evidence of a growth-promoting role for RHBDD1 in colorectal cancer and may aid the development of tumor biomarkers or antitumor therapeutics.
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