Faecal pyruvate kinase isoenzyme type M2 for colorectal cancer screening:A meta-analysis

AIM:To present a critical discussion of the efficacy of the faecal pyruvate kinase isoenzyme type M2(faecal M2-PK) test for colorectal cancer(CRC) screening based on the currently available studies.METHODS:A literature search in PubMed and Embase was conducted using the following search terms:fecal Tumor M2-PK,faecal Tumour M2-PK,fecal M2-PK,faecal M2-PK,fecal pyruvate kinase,faecal pyruvate kinase,pyruvate kinase stool and M2-PK stool.RESULTS:Stool samples from 704 patients with CRC and from 11 412 healthy subjects have been investigated for faecal M2-PK concentrations in seventeen independent studies.The mean faecal M2-PK sensitivity was 80.3%;the specificity was 95.2%.Four studies compared faecal M2-PK head-to-head with guaiacbased faecal occult blood test(gFOBT).Faecal M2PK demonstrated a sensitivity of 81.1%,whereas the gFOBT detected only 36.9% of the CRCs.Eight independent studies investigated the sensitivity of faecal M2-PK for adenoma(n = 554),with the following sensitivities:adenoma < 1 cm in diameter:25%;adenoma > 1 cm:44%;adenoma of unspecified diameter:51%.In a direct comparison with gFOBT of adenoma > 1 cm in diameter,47% tested positive with the faecal M2-PK test,whereas the gFOBT detected only 27%.CONCLUSION:We recommend faecal M2-PK as a routine test for CRC screening.Faecal M2-PK closes a gap in clinical practice because it detects bleeding and nonbleeding tumors and adenoma with high sensitivity and specificity.

Tumor pyruvate kinase M2:A promising molecular target of gastrointestinal cancer

Gastrointestinal(GI) cancer is one of the most common causes of cancer-related deaths worldwide.Tumor markers are valuable in detecting post-surgical recurrence or in monitoring response to chemotherapy.Pyruvate kinase isoform M2(PKM2),a glycolytic enzyme catalyzing conversion of phosphoenolpyruvate(PEP) to pyruvate,confers a growth advantage to the tumor cells and enables them to adapt to the tumor microenvironment.In this review,we have summarized current research on the expression and regulation of PKM2 in tumor cells,and its potential role in GI carcinogenesis and progression.Furthermore,we have also discussed the potential of PKM2 as a diagnostic and screening marker,and a therapeutic target in GI cancer.

Overexpressed PKM2 promotes macrophage phagocytosis and atherosclerosis

Background:The expression of pyruvate kinase muscle 2(PKM2)is augmented in macrophages of patients with atherosclerotic coronary artery disease.The role of PKM2 in atherosclerosis is to be determined.Methods:Global and myeloid cell-specific PKM2 knock-in mice with ApoE^(-/-)background(ApoE^(-/-),PKM2^(KI/KI)and Lyz2-cre,ApoE^(-/-),and PKM2^(flox/flox))were produced to evaluate the clinical significance of PKM2 in atherosclerosis development.Wild-type and PKM2 knock-in macrophages were isolated to assess the function of PKM2 in macrophage phagocytosis.Atherosclerotic mice were treated with PKM2 inhibitor shikonin(SKN)to evaluate the therapeutic potential of PKM2 suppression in atherosclerosis.Results:Oxidized low-density lipoprotein(oxLDL)upregulated PKM2 in macrophages.PKM2 in return promoted the uptake of oxLDL by macrophages.Overexpressed PKM2 accelerated atherosclerosis in mice.SKN blocked the progress of mouse atherosclerosis.Conclusions:PKM2 accelerates macrophage phagocytosis and atherosclerosis.Targeting PKM2 is a potential therapy for atherosclerosis.

SGOL1通过调节PKM2促进肺癌细胞增殖和侵袭

Shugoshin-1(SGOL1)是酵母Shugoshin的人类同源物之一,位于着丝粒区域,能够通过阻止着丝粒内聚复合物早熟分裂维持染色体稳定。近年来,SGOL1在肿瘤中的作用受到关注,但它在肺癌中的功能尚不清楚。本研究基于TCGA数据库分析发现,SGOL1在肺癌组织中高表达(n=529,P<0.00001),并与患者的不良预后呈正相关(P=0.0049)。qRT-PCR和Western印迹结果证实:SGOL1在肺癌细胞系表达水平均较正常肺上皮细胞的升高。在肺癌A549和NCI-H2405细胞系中,敲低SGOL1表达水平后,Cell Counting Kit-8(CCK8)实验、平板克隆实验、划痕愈合实验、Transwell实验结果分别提示,细胞的增殖、克隆形成、迁移、侵袭能力下降(P<0.05)。同时本研究发现,在TCGA数据中,丙酮酸激酶肌肉同工酶2(PKM2)和SGOL1的表达呈正相关性(r=0.38,P=0)。Western印迹检测显示,在肺癌细胞A549和NCI-H2405中,敲低SGOL1能下调PKM2的表达水平。此外,功能回补实验证实,过表达PKM2能部分逆转敲低SGOL1对肺癌细胞的增殖、克隆形成、迁移和侵袭能力的抑制作用。因此,本研究表明,SGOL1可能通过调节PKM2促进肺癌细胞的增殖和侵袭。本研究为SGOL1在肺癌中的作用机制提供理论依据。

M2 pyruvate kinase enhances HIV-1 transcription from its long terminal repeat

Both thymocytes and tumor cells express M2 type isoenzyme of pyruvate kinase(M2PK),which is different from R type isoenzyme of pyruvate kinase(RPK)that is expressed in erythrocytes.In this report,the effect of RPK and M2PK on the transcription of human immunodeficiency virus type 1(HIV-1)was tested.The results indicated that M2PK could enhance HIV-1 transcription from its long terminal repeat(LTR)promoter,while RPK did not have such an effect.Specific down-regulation of M2PK could inhibit HIV-1 transcription from its LTR region.Furthermore,it was found that the C terminal region of M2PK is responsible for this effect.Collectively,the cellular factor M2PK that is expressed in thymocytes could facilitate the transcription of HIV-1.

丙酮酸激酶肌异构体2调控免疫细胞代谢的研究进展

丙酮酸激酶肌异构体2(pyruvate kinase muscle isoform 2,PKM2)是糖酵解的关键限速酶,也是免疫细胞代谢的重要调节因子。PKM2已被证明在多种炎症性疾病中过表达,并促进免疫细胞和炎症细胞的代谢和生物大分子的合成。PKM2的表达转变且激发了科研工作者对PKM2在免疫细胞中的作用机制和在炎症性疾病中治疗潜力的研究方向。此外,PKM2的结构和功能受一些激活剂和抑制剂的影响,研究人员揭示了PKM2的小分子激活剂和抑制剂的具体作用机制。免疫代谢重编程在炎症的发生、发展中起着至关重要的作用,因此,有必要明确PKM2在免疫代谢重编程中的作用。现就PKM2在不同免疫细胞中的作用,以及PKM2在免疫代谢重编程中的分子机制作一综述,期望有助于研究人员更好地了解PKM2的分子机制,从而帮助临床医生制定治疗策略。

降糖速度对2型糖尿病合并冠心病患者肌酸激酶同工酶和肌红蛋白的影响

通过对151例2型糖尿病合并冠心病（T2DMC）患者和142例2型糖尿病患者在降糖过程中肌酸激酶同工酶（CKMB）和肌红蛋白水平变化的研究，寻找2型糖尿病患者合理的降糖速度。2型糖尿病组CKMB水平在随访时较降糖前后均下降（P〈0．05），当空腹或餐后2h降糖速度≤6mmol·L^-1·d^-1时，CKMB与肌红蛋白水平随访时较降糖前均有显著下降（P〈0．05），当空腹降糖速度〉6mmol·L^-1·d^-1时，CKMB水平降糖后较降糖前显著升高（P〈0．05）；T2DMC组空腹或餐后2h降糖速度≤4mmol·L^-1·d^-1时，CKMB与肌红蛋白水平随访时较降糖前显著下降（P〈0．05或P〈O．01），当空腹降糖速度〉4mmol·L^-1·d^-1时，CKMB与肌红蛋白水平随访时较降糖前显著升高（P〈0．05）。

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.