Targeting LncRNA LLNLR-299G3.1 with antisense oligonucleotide inhibits malignancy of esophageal squamous cell carcinoma cells in vitro and in vivo

Accumulating evidence has indicated that long non-coding RNAs(lncRNAs)play critical roles in the development and progression of cancers,including esophageal squamous cell carcinoma(ESCC).However,the mechanisms of lncRNAs in ESCC are still incompletely understood and therapeutic attempts for in vivo targeting cancer-associated lncRNA remain a challenge.By RNA-sequencing analysis,we identified that LLNLR-299G3.1 was a novel ESCC-associated lncRNA.LLNLR-299G3.1 was up-regulated in ESCC tissues and cells and promoted ESCC cell proliferation and invasion.Silencing of LLNLR-299G3.1 with ASO(antisense oligonucleotide)resulted in opposite effects.Mechanistically,LLNLR-299G3.1 bound to cancerassociated RNA binding proteins and regulated the expression of cancer-related genes,including OSM,TNFRSF4,HRH3,and SSTR3.ChIRP-seq(chromatin isolation by RNA purification and sequencing)revealed that these genes contained enriched chromatin binding sites for LLNLR-299G3.1.Rescue experiments confirmed that the effects of LLNLR-299G3.1 on ESCC cell proliferation were dependent on interaction with HRH3 and TNFRSF4.Therapeutically,intravenous delivery of placental chondroitin sulfate A binding peptide-coated nanoparticles containing antisense oligonucleotide(pICSA-BP-ANPs)strongly inhibited ESCC tumor growth and significantly improved animal survival in vivo.Overall,our results suggest that LLNLR-299G3.1 promotes ESCC malignancy through regulating gene-chromatin interactions and targeting ESCC by pICSA-BP-ANPs may be an effective strategy for the treatment of lncRNA-associated ESCC.

INFINITELY MANY SOLUTIONS WITH PEAKS FOR A FRACTIONAL SYSTEM IN R^N

In this article,we consider the following coupled fractional nonlinear Schrödinger system in R^{(−Δ)su+P(x)u=μ1|u|^2p−2u+β|u|p|u|p−2u,x∈RN,(−Δ)sv+Q(x)v=μ2|v|^2p−2v+β|v|p|v|p−2v,x∈RN,u,v∈Hs(RN),where N≥2,0<s<1,1<p<NN−2s,μ1>0,μ2>0 andβ∈R is a coupling constant.We prove that it has infinitely many non-radial positive solutions under some additional conditions on P(x),Q(x),p andβ.More precisely,we will show that for the attractive case,it has infinitely many non-radial positive synchronized vector solutions,and for the repulsive case,infinitely many non-radial positive segregated vector solutions can be found,where we assume that P(x)and Q(x)satisfy some algebraic decay at infinity.

Quantitative properties of ground-states to an M-coupled system with critical exponent in R^N

In this paper, we consider the ground-states of the following M-coupled system:where p_(ij)+q_(ij)=2*:=2 N/(N-2)(N≥3). We prove the existence of ground-states to the M-coupled system. At the same time, we not only give out the characterization of the ground-states, but also study the number of the ground-states, containing the positive ground-states and the semi-trivial ground-states, which may be the first result studying the number of not only positive ground-states but also semi-trivial ground-states.