同源盒转录因子CDX2与Y染色体决定因子SOX9在肠上皮化生及胃癌组织中的表达

目的:研究同源盒转录因子CDX2和Y染色体决定因子SOX9在肠上皮化生(intestinal metaplasia,IM)及胃癌组织中的表达,探讨CDX2和SOX9在IM发生、进展及胃癌发生、发展中的作用及相互关系.方法:选取慢性萎缩性胃炎(chronic atrophic gastritis,CAG)伴IM 24例、癌旁IM 17例、胃癌组织50例,用HE染色对IM及胃癌进行组织学分型,免疫组化法观察CDX2、SOX9蛋白在上述各种胃黏膜组织中的表达,研究二者表达与胃癌临床病理学特征之间的关系.结果:CDX2蛋白表达阳性率在CAG伴IM组、癌旁IM组和胃癌组分别为87.50％、76.47％和62.00％,CAG伴IM组显著高于胃癌组(P＜0.05),CAG伴IM组与癌旁IM组、癌旁IM组与胃癌组之间比较无统计学差异(P＞0.05),肠型胃癌显著高于弥漫型胃癌(77.78％ vs 43.48％,P=0.013).CDX2蛋白在胃癌中的表达与胃癌临床分期、分化程度、Lauren分型及是否有浆膜浸润等有关.SOX9蛋白表达阳性率,在CAG伴IM组、癌旁IM组及胃癌组分别为54.17％、70.59％、80.00％,CAG伴IM组显著低于胃癌组(P＜0.05),CAG伴IM组与癌旁IM组、癌旁IM组与胃癌组之间比较无统计学差异(P＞0.05),肠型胃癌显著高于弥漫型胃癌(92.59％ vs 65.22％,P=0.040).SOX9蛋白在胃癌中的表达与胃癌分化程度、临床分期、Lauren分型和是否淋巴结转移等有关联.胃癌组织中CDX2和SOX9的阳性表达存在显著性负相关(r=-0.391,X2=5.778,P=0.016).结论:CDX2、SOX9在IM及肠型胃癌的发生中可能有重要作用,可做为IM及肠型胃癌预测的特异性指标之一.二者可能在胃癌进展及浸润转移过程中起重要作用,联合检测对选择合适治疗方式及预后判断具有重要价值.     

结直肠癌肿瘤干细胞标志物的研究进展

肿瘤干细胞与恶性肿瘤复发、耐药等生物学过程密切相关,是治疗恶性肿瘤的新靶点.寻找稳定性高、特异性强、实用性好的肿瘤干细胞标志物,清除恶性肿瘤中的肿瘤干细胞有望彻底根治恶性肿瘤.本文综述了结直肠癌中比较公认的肿瘤干细胞标志物CD44和潜在的肿瘤干细胞标志物LGR5、Bmi1、SOX2、Nanog的研究进展,为靶向治疗结直肠癌提供了参考依据.     

SOX2 promotes tumor metastasis by stimulating epithelial-to-mesenchymal transition via regulation of WNT/β-catenin signal network

SOX2 was reported to promote metastasis in various tumor tissues; however the underlying mechanisms remain elusive. Here, we disclosed that SOX2 improves metastasis of breast and prostate cancer cells by promoting epithelial-to-mesenchymal transition (EMT) through WNT/β-catenin, but not TGF-β or Snail1 signaling. Dual luciferase assay and chromatin immunoprecipitation revealed activation and binding of SOX2 on promoter region of β-catenin. In addition, SOX2 affects the protein expression levels of DKK3, DVL1 and DVL3, which are regulators or downstream molecules of WNT signaling. Taken together, our findings demonstrated β-catenin as one of vital downstream molecules that mediate the EMT induced by SOX2.     

MiR-429 is an independent prognostic factor in colorectal cancer and exerts its anti-apoptotic function by targeting SOX2

Emerging evidence has demonstrated that microRNAs (miRNAs) can act as oncogenes or tumor suppressors to participate in cancer development. In this study, we found that miR-429 expression was up-regulated in human colorectal cancer (CRC) tissues, and the high miR-429 expression was significantly associated with tumor size, lymph node metastasis and poor prognosis. Functionally, miR-429 overexpression suppressed cell apoptosis by directly targeting SOX2 in HT-29 cells. Taken together, our data suggest for the first time that miR-429 could play an oncogenic role in the cellular processes of CRC and represent a novel prognostic biomarker for CRC.     

De novo dominant mutation of SOX10 gene in a Chinese family with Waardenburg syndrome type II

Objective

Waardenburg syndrome is a rare genetic disorder, inherited as an autosomal dominant trait. The condition is characterized by sensorineural hearing loss and pigment disturbances of the hair, skin, and iris. The de novo mutation in the SOX10 gene, responsible for Waardenburg syndrome type II, is rarely seen. The present study aimed to identify the genetic causes of Waardenburg syndrome type II in a Chinese family.

Methods

Clinical and molecular evaluations were conducted in a Chinese family with Waardenburg syndrome type II.

Results

A novel SOX10 heterozygous c.259-260delCT mutation was identified. Heterozygosity was not observed in the parents and sister of the proband, indicating that the mutation has arisen de novo. The novel frameshift mutation, located in exon 3 of the SOX10 gene, disrupted normal amino acid coding from Leu87, leading to premature termination at nucleotide 396 (TGA). The high mobility group domain of SOX10 was inferred to be partially impaired.

Conclusion

The novel heterozygous c.259-260delCT mutation in the SOX10 gene was considered to be the cause of Waardenburg syndrome in the proband. The clinical and genetic characterization of this family would help elucidate the genetic heterogeneity of SOX10 in Waardenburg syndrome type II. Moreover, the de novo pattern expanded the mutation data of SOX10.     

SOX4在消化系统恶性肿瘤中的研究进展

SOX4是SOX家族C组亚科的成员,它可能通过赋予癌细胞生存、迁移和侵袭能力来促进肿瘤发生发展。目前已有多种证据支持SOX4是一种重要的癌基因的观点。SOX4在多种恶性肿瘤中过表达,包括消化系统肿瘤,而消化系统肿瘤是发展中国家癌症患者死亡的最常见原因。近年来,SOX4引起恶性转化的分子机制及其与消化系统肿瘤的关系成为研究的焦点和前沿领域。本文就SOX4在消化系统肿瘤中的研究现状进行综述。     

Induced Pluripotent Reprogramming from Promiscuous Human Stemness‐Related Factors

Ectopic expression of pluripotency gene sets provokes nuclear reprogramming in permissive somatic tissue environments, generating nduced pluripotent stem (iPS) cells. The evolutionary conserved function of sternness orthologs was tested here through interspecies transduction. A spectrum of human immunodeficiency virus (HIV)‐based lentiviral vectors was designed, and point mutations in the HIV‐1 capsid region were identified for efficient infectivity and expanded transspecies tropism. Human pluripotent gene sequences, OCT3/4, SOX2, KLF4, and c‐MYC, packaged into engineered lentiviral expression vectors achieved consistent expression in nonhuman fibroblasts. Despite variation in primary amino acid sequence between species, introduction of human pluripotent genes produced cell lines with embryonic stem cell‐like morphology. Transduced fibroblasts differentiated in vitro into all three germ layers according to gastrulation gene expression profiles, and formed in vivo teratoma with multilineage potential. Reprogrammed progeny incorporated into nonhuman morula to produce blastomeres capable of developing into chimeric embryos with competent organogenesis. This model system establishes a prototypic approach to examine consequences of human sternness factors‐induced reprogramming in the context of normal embryonic development by exploiting nonhuman early‐stage embryos. Thus, ectopic xenotransduction across species unmasks the promiscuous nature of sternness induction, suggesting evolutionary selection of core processes for somatic tissue reprogramming.