Protein arginine methyltransferase 1 coordinates the epithelial-mesenchymal transition/proliferation dichotomy in gastric cancer cells.

Protein arginine methyltransferase 1 (PRMT1) is up-regulated and promotes migration, invasion and proliferation in wide range of cancers. However, we for the first time identify that PRMT1 promotes migration and invasion and inhibits proliferation in gastric cancer cells, a phenomenon called "migration-proliferation dichotomy". First, we find that PRMT1 overexpression promotes migration and invasion and inhibits proliferation, whereas PRMT1 knockdown reverses the above abilities. Next, PRMT1 reduces the expression of epithelial marker E-cadherin and increases the expression of mesenchymal markers including N-cadherin, Vimentin, snail and ß-catenin in gastric cancer cells. Furthermore, our studies show that PRMT1 silencing promotes the phosphorylation of LATS1, and then induces YAP phosphorylation, while overexpression of PRMT1 down-regulates the phosphorylation of LATS1 and YAP, indicating that PRMT1 inhibits EMT probably via Hippo signaling. Collectively, the present study reveals important roles of PRMT1 in progression of gastric cancer. Given the dual functions of PRMT1, it is as a potential drug target of gastric cancer with extreme caution.

LncRNA UCA1 promotes migration and invasion in pancreatic cancer cells via the Hippo pathway.

Although overexpression of the long non-coding RNA (lncRNA) UCA1 has been implicated in several human cancers, its biological function in pancreatic cancer remains to be clarified. In this study, we reported that UCA1 expression was significantly increased in pancreatic cancer tissues and correlated with clinicopathological features, tumor stage, and poorer patient outcome. We further showed that UCA1 promoted cell migration and invasion of pancreatic cancer cells. Importantly, we found that UCA1 overexpression inhibited YAP phosphorylation, and increased YAP expression. Mechanistically, UCA1 interacted with MOB1, Lats1, and YAP, forming shielding composites. Moreover, we demonstrated that UCA1 increased YAP nuclear localization and stabilization, and improved TEAD luciferase activity. In turn, YAP promotes UCA1 expression. Collectively, the present study provides insights into the mechanistic regulation of UCA1 promoting pancreatic cancer progression through the Hippo signaling pathway. UCA1 may serve as a candidate biomarker for poor prognosis and a target for new pancreatic cancer therapies.

Exosomes Derived From Human Adipose-Derived Stem Cells Inhibit Lipogenesis Involving Hedgehog Signaling Pathway.

Since obesity impairs wound closure and adipose-derived exosomes (ADEs) regulate wound healing in clinical applications, we hypothesized that ADEs may inhibit adipogenesis of adipose-derived stem cells (ADSCs) to reduce the adverse effects of obesity on wound healing. Hedgehog (Hh) signaling has been previously shown to inhibit adipogenesis in ADSCs. The present study aimed to determine the role of ADEs in the adipogenesis of ADSCs and the Hh signaling pathway. ADSCs collected from human adipose tissues were co-cultured with ADEs and treated with an adipogenic inducer. qRT-PCR showed that ADEs could inhibit adipogenic differentiation of ADSCs and activate Hh signaling. The differences in the mRNA expression profiles of genes related to Hh signaling between the groups that were exposed to either high fat or low fat indicated that increased Hh signaling activation is necessary but not sufficient to inhibit adipogenic differentiation in the ADSC differentiation process. The Hh signaling pathway can be activated effectively by ADEs, especially during high-fat exposure after treatment with ADEs. Oil Red O staining of adipocytes suggested that ADEs inhibited not only adipogenic differentiation, but also lipogenesis in ADSCs. Overall, targeted activation of Hh signaling by ADEs reduced lipid accumulation in ADSCs and may be explored for clinical applications.

Comparative effectiveness of extracorporeal shock wave, ultrasound, low-level laser therapy, noninvasive interactive neurostimulation, and pulsed radiofrequency treatment for treating plantar fasciitis: A systematic review and network meta-analysis.

BACKGROUND: Plantar fasciitis is one of the most common causes of adult heel pain. The aim of this study is to comprehensively compare the effectiveness of various therapies for plantar fasciitis using network meta-analysis. METHODS: Studies were comprehensively searched on Embase, MEDLINE via PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and the Physiotherapy Evidence Database (PEDro) up to December 4, 2017. Randomized controlled trials that used extracorporeal shock wave therapy, ultrasound, ultrasound-guided pulsed radiofrequency treatment (UG-PRF), intracorporeal pneumatic shock therapy (IPST), low-level laser therapy (LLLT), and noninvasive interactive neurostimulation (NIN) for the treatment of plantar fasciitis were included. The primary outcome is change in pain relief. Risk of bias was assessed using the Cochrane risk of bias tool. Quality assessment was performed using the GRADE system. RESULTS: Nineteen trials with 1676 patients with plantar fasciitis plantar fasciitis were included. In the pair-wise meta-analysis, radial extracorporeal shock wave therapy (RSW), LLLT, and IPST showed a significant pooled reduction in the visual analogue scale (VAS) compared with placebo at 0 to 6 weeks [mean difference (MD) = 6.60, 95% confidence interval (CI): (6.04, -7.16); MD = 2.34, 95% CI: (1.60, 3.08); MD = 2.24, 95% CI: (1.44, 3.04), respectively]. Compared with placebo, UG-PRF [MD = 2.31, 95% CI: (1.26, 3.36)] and high-intensity focused extracorporeal shock wave (H-FSW) [MD = 0.82, 95% CI: (0.20, 1.45)] showed superior pain-relieving effects at 2 to 4 months; UG-PRF [MD = 1.11, 95% CI: (0.07, 2.15)] and IPST [MD = 4.92, 95% CI: (4.11, 5.73)] showed superior effects at 6 to 12 months. In the network meta-analysis, only RSW induced significant pain reduction compared with placebo at 0 to 6 weeks [MD = 3.67, 95% CI: (0.31, 6.9)]. No significant differences were found for the 2 to 4-month and 6 to 12-month periods because of the wide 95% CIs. CONCLUSIONS: We recommend treating plantar fasciitis with RSW. The commonly used ultrasound and focused extracorporeal shock wave (FSW) therapies can be considered as alternative treatment candidates. IPST, NIN, and LLLT may potentially be better alternatives, although their superiority should be confirmed by additional comprehensive evidence.PROSPERO registration number: PROSPERO (CRD42015017353).