Posttranslational modifications(PTMs)of proteins,including chromatin modifiers,play crucial roles in the dynamic alteration of various protein properties and functions including stem-cell properties.However,the roles of Lymphoid-specific helicase(LSH),a DNA methylation modifier,in modulating stem-like properties in cancer are still not clearly clarified.Therefore,exploring PTMs modulation of LSH activity will be of great significance to further understand the function and activity of LSH.Here,we demonstrate that LSH is capable to undergo PTMs,including methylation and phosphorylation.The arginine methyltransferase PRMT5 can methylate LSH at R309 residue,meanwhile,LSH could as well be phosphorylated by MAPK1 kinase at S503 residue.We further show that the accumulation of phosphorylation of LSH at S503 site exhibits downregulation of LSH methylation at R309 residue,which eventually promoting stem-like properties in lung cancer.Whereas,phosphorylation-deficient LSH S503A mutant promotes the accumulation of LSH methylation at R309 residue and attenuates stem-like properties,indicating the critical roles of LSH PTMs in modulating stem-like properties.Thus,our study highlights the importance of the crosstalk between LSH PTMs in determining its activity and function in lung cancer stem-cell maintenance.
Na LiuRui YangYing ShiLing ChenYating LiuZuli WangShouping LiuLianlian OuyangHaiyan WangWeiwei LaiChao MaoMin WangYan ChengShuang LiuXiang WangHu ZhouYa CaoDesheng XiaoYongguang Tao
Tumor suppressor genes cooperate with each other in tumors.Three important tumor suppressor proteins,retinoblastoma(Rb),p53,phosphatase,and tensin homolog deleted on chromosome ten(PTEN)are functionally associated and they regulated by posttranslational modification(PTMs)as well.PTMs include phosphorylation,SUMOylation,acetylation,and other novel modifications becoming growing appreciated.Because most of PTMs are reversible,normal cells use them as a switch to control the state of cells being the resting or proliferating,and PTMs also involve in cell survival and cell cycle,which may lead to abnormal proliferation and tumorigenesis.Although a lot of studies focus on the importance of each kind of PTM,further discoveries shows that tumor suppressor genes(TSGs)form a complex“network”by the interaction of modification.Recently,there are several promising strategies for TSGs for they change more frequently than carcinogenic genes in cancers.We here review the necessity,characteristics,and mechanisms of each kind of post-translational modification on Rb,p53,PTEN,and its influence on the precise and selective function.We also discuss the current antitumoral therapies of Rb,p53 and PTEN as predictive,prognostic,and therapeutic target in cancer.
The trillions of microorganisms in the gut microbiome have attracted much attention recently owing to their sophisticated and widespread impacts on numerous aspects of host pathophysiology.Remarkable progress in large-scale sequencing and mass spectrometry has increased our understanding of the influence of the microbiome and/or its metabolites on the onset and progression of extraintestinal cancers and the efficacy of cancer immunotherapy.Given the plasticity in microbial composition and function,microbial-based therapeutic interventions,including dietary modulation,prebiotics,and probiotics,as well as fecal microbial transplantation,potentially permit the development of novel strategies for cancer therapy to improve clinical outcomes.Herein,we summarize the latest evidence on the involvement of the gut microbiome in host immunity and metabolism,the effects of the microbiome on extraintestinal cancers and the immune response,and strategies to modulate the gut microbiome,and we discuss ongoing studies and future areas of research that deserve focused research efforts.
Ziying ZhangHaosheng TangPeng ChenHui XieYongguang Tao
Nasopharyngeal carcinoma(NPC)is a malignant tumor that usually occurs in people from Southeast Asia and Southern China.NPC is prone to migration and invasion,leading to poor prognosis.A large number of circular RNAs(circ RNAs)exacerbate the process of metastasis in NPC;however,their underlying mechanisms remain unclear.We found that the circular RNA circ CCNB1,encoded by the oncogene CCNB1,was downregulated in NPC biopsies and cell lines.In vitro assays show that circ CCNB1 inhibits NPC cell migration and invasion.Moreover,circ CCNB1 induces a protein,nuclear factor 90(NF90),to bind and prolong the half-life of tight junction protein 1(TJP1)m RNA.Upregulation of TJP1 enhances tight junctions between cancer cells and inhibits NPC cell migration and invasion.This study reveals a novel biological function of circ CCNB1 in the migration and invasion of NPC by enhancing the tight junctions of cancer cells by binding to NF90 proteins and TJP1 m RNA,and may provide a potential therapeutic target for NPC.
Nasopharyngeal carcinoma （NPC） is a squamous-cell carcinoma that arises in the epithelial lining of the nasopharynx [1]. This neoplasm has a notable ethnic and geographic distribution, being of high prevalence in southern China but rare in other parts of the world [2]. Familial clustering of NPC has been observed in diverse populations [3]. Elevated levels of circulating free Epstein-Barr virus （EBV） DNA and EBV-related antibodies in sera, as well as EBV DNA in tumor ceils, have been consistently detected in individuals with NPC [4,5].
Actin filament associated protein 1 antisense RNA 1(named AFAP1-AS1)is a long non-coding RNA and overexpressed in many cancers.This study aimed to identify the role and mechanism of AFAP1-AS1 in lung cancer.The AFAP1-AS1 expression was firstly assessed in 187 paraffin-embedded lung cancer and 36 normal lung epithelial tissues by in situ hybridization.The migration and invasion abilities of AFAP1-AS1 were investigated in lung cancer cells.To uncover the molecular mechanism about AFAP1-AS1 function in lung cancer,we screened proteins that interact with AFAP1-AS1 by RNA pull down and the mass spectrometry analyses.AFAP1-AS1 was highly expressed in lung cancer clinical tissues and its expression was positively correlated with lung cancer patients'poor prognosis.In vivo experiments confirmed that AFAP1-AS1 could promote lung cancer metastasis.AFAP1-AS1 promoted lung cancer cells migration and invasion through interacting with Smad nuclear interacting protein 1(named SNIP1),which inhibited ubiquitination and degradation of c-Myc protein.Upregulation of c-Myc molecule in turn promoted the expression of ZEB1,ZEB2,and SNAIL gene,which ultimately enhanced epithelial to mesenchymal transition(EMT)and lung cancer metastasis.Understanding the molecular mechanism by which AFAP1-AS1 promotes lung cancer's migration and invasion may provide novel therapeutic targets for lung cancer patients'early diagnosis and therapy.
