Roles of PTBP1 in alternative splicing, glycolysis, and oncogensis

Polypyrimidine tract-binding protein 1(PTBP1)plays an essential role in splicing and is expressed in almost all cell types in humans,unlike the other proteins of the PTBP family.PTBP1 mediates several cellular processes in certain types of cells,including the growth and differentiation of neuronal cells and activation of immune cells.Its function is regulated by various molecules,including micro RNAs(mi RNAs),long non-coding RNAs(lnc RNAs),and RNA-binding proteins.PTBP1 plays roles in various diseases,particularly in some cancers,including colorectal cancer,renal cell cancer,breast cancer,and glioma.In cancers,it acts mainly as a regulator of glycolysis,apoptosis,proliferation,tumorigenesis,invasion,and migration.The role of PTBP1 in cancer has become a popular research topic in recent years,and this research has contributed greatly to the formulation of a useful therapeutic strategy for cancer.In this review,we summarize recent findings related to PTBP1 and discuss how it regulates the development of cancer cells.

Demystifying the manipulation of host immunity, metabolism, and extraintestinal tumors by the gut microbiome

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.

Rab22a-NeoF1:a promising target for osteosarcoma patients with lung metastasis

Osteosarcoma is the most common primary malignant bone tumor among adolescents and children,with high level of lung metastasis and poor prognosis.The treatment of metastatic cases remains a challenge in the clinic,leading to the dramatically decreased survival rate.However,the molecular mechanisms are still unclear.A recent article by Kang et al.demonstrated how chromosomal translocations in osteosarcoma facilitated lung metastasis,and shed new light on its therapeutic strategies1(Fig.1).

Regulating tumor suppressor genes:post-translational modifications

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.

Signaling pathways in cancer metabolism:mechanisms and therapeutic targets

A wide spectrum of metabolites(mainly,the three major nutrients and their derivatives)can be sensed by specific sensors,then trigger a series of signal transduction pathways and affect the expression levels of genes in epigenetics,which is called metabolite sensing.Life body regulates metabolism,immunity,and inflammation by metabolite sensing,coordinating the pathophysiology of the host to achieve balance with the external environment.Metabolic reprogramming in cancers cause different phenotypic characteristics of cancer cell from normal cell,including cell proliferation,migration,invasion,angiogenesis,etc.Metabolic disorders in cancer cells further create a microenvironment including many kinds of oncometabolites that are conducive to the growth of cancer,thus forming a vicious circle.At the same time,exogenous metabolites can also affect the biological behavior of tumors.Here,we discuss the metabolite sensing mechanisms of the three major nutrients and their derivatives,as well as their abnormalities in the development of various cancers,and discuss the potential therapeutic targets based on metabolite-sensing signaling pathways to prevent the progression of cancer.

The cross-talk between methylation and phosphorylation in lymphoid-specific helicase drives cancer stem-like properties

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.