Sun Honggang, He Liqin, Ma Lan, Lu Tao, Wei Jianguo, Xie Kejie, Wang Xingmu
Clinical Laboratory Center, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang Province, China.
Department of Rehabilitation, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang Province, China.
Oncotarget. 2017 Nov 30;8(66):110552-110565. doi: 10.18632/oncotarget.22819. eCollection 2017 Dec 15.
Thyroid cancer is one of the most prevalent endocrine neoplasm. The present study examined the effects of Colorectal Neoplasia Differentially Expressed (CRNDE) on the progression of papillary thyroid cancer (PTC), and explored the underlying molecular mechanisms. Quantitative real-time PCR was used to detect CRNDE, miR-384 and pleiotrophin (PTN) mRNA expression. Western blot was used to measure PTN protein levels. Cell proliferation, cell growth, cell invasion and migration of PTC cells were determined by CCK-8, colony formation, transwell invasion and migration assays, respectively. CRNDE was up-regulated in PTC tissues and cell lines. Overexpression of CRNDE promoted BCPAP cell proliferation, invasion and migration, while knock-down of CRNDE suppressed K1 cell proliferation, invasion and migration. CRNDE negatively regulated the expression of miR-384 in PTC cells, which was further confirmed by luciferase reporter assay. MiR-384 was down-regulated and inversely correlated with CRNDE expression in PTC tissues. MiR-384 suppressed cell proliferation, invasion and migration in PTC cells, and enforced expression of miR-384 attenuated the oncogenic effects of CRNDE in PTC cells. PTN was predicted as a downstream target of miR-384, which was confirmed by luciferase reporter assay, and PTN was up-regulated in PTC tissues, and was negatively correlated with miR-384 expression and positively correlated with CRNDE expression in PTC tissues. In summary, our results suggested that the CRNDE/miR-384/PTN axis may play an important role in the regulation of PTC progression, which provides us with new insights into understanding the PTC.
甲状腺癌是最常见的内分泌肿瘤之一。本研究检测了结直肠癌差异表达基因(CRNDE)对甲状腺乳头状癌(PTC)进展的影响,并探讨了其潜在的分子机制。采用定量实时PCR检测CRNDE、miR - 384和多效生长因子(PTN)mRNA表达。采用蛋白质免疫印迹法检测PTN蛋白水平。分别通过CCK - 8法、集落形成试验、transwell侵袭和迁移试验检测PTC细胞的增殖、生长、侵袭和迁移能力。CRNDE在PTC组织和细胞系中上调。CRNDE过表达促进BCPAP细胞增殖、侵袭和迁移,而敲低CRNDE则抑制K1细胞增殖、侵袭和迁移。CRNDE在PTC细胞中负向调节miR - 384的表达,荧光素酶报告基因试验进一步证实了这一点。miR - 384在PTC组织中表达下调,且与CRNDE表达呈负相关。miR - 384抑制PTC细胞的增殖、侵袭和迁移,miR - 384的强制表达减弱了CRNDE在PTC细胞中的致癌作用。PTN被预测为miR - 384的下游靶点,荧光素酶报告基因试验证实了这一点,PTN在PTC组织中上调,在PTC组织中与miR - 384表达呈负相关,与CRNDE表达呈正相关。综上所述,我们的结果表明CRNDE/miR - 384/PTN轴可能在PTC进展的调控中起重要作用,这为我们理解PTC提供了新的见解。