Gastroenterology Division and Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Cancer Res. 2011 Jun 15;71(12):4260-8. doi: 10.1158/0008-5472.CAN-10-4637. Epub 2011 Apr 21.
LIN28B is a homologue of LIN28 that induces pluripotency when expressed in conjunction with OCT4, SOX2, and KLF4 in somatic fibroblasts. LIN28B represses biogenesis of let-7 microRNAs and is implicated in both development and tumorigenesis. Recently, we have determined that LIN28B overexpression occurs in colon tumors. We conducted a comprehensive analysis of LIN28B protein expression in human colon adenocarcinomas. We found that LIN28B overexpression correlates with reduced patient survival and increased probability of tumor recurrence. To elucidate tumorigenic functions of LIN28B, we constitutively expressed LIN28B in colon cancer cells and evaluated tumor formation in vivo. Tumors with constitutive LIN28B expression exhibit increased expression of colonic stem cell markers LGR5 and PROM1, mucinous differentiation, and metastasis. Together, our findings point to a function for LIN28B in promoting colon tumor pathogenesis, especially metastasis.
LIN28B 是 LIN28 的同源物，当其与 OCT4、SOX2 和 KLF4 在体成纤维细胞中表达时，可诱导多能性。LIN28B 抑制 let-7 微 RNA 的生物发生，与发育和肿瘤发生均有关。最近，我们已经确定 LIN28B 在结肠癌中过度表达。我们对人结肠腺癌中 LIN28B 蛋白表达进行了全面分析。我们发现 LIN28B 的过度表达与患者生存时间缩短和肿瘤复发概率增加相关。为了阐明 LIN28B 的致癌功能，我们在结肠癌细胞中持续表达 LIN28B，并评估体内肿瘤形成情况。持续表达 LIN28B 的肿瘤表现出结肠干细胞标志物 LGR5 和 PROM1、黏液分化和转移的表达增加。综上所述，我们的研究结果表明 LIN28B 在促进结肠肿瘤发病机制，特别是转移方面发挥作用。
