Department of Pathology, Stony Brook University, Stony Brook, NY.
Clin Colorectal Cancer. 2013 Dec;12(4):261-6. doi: 10.1016/j.clcc.2013.06.003. Epub 2013 Sep 5.
Long intergenic noncoding RNAs (lincRNAs) have been shown to be novel regulators for both transcription and posttranscriptional/translation. One of them, lincRNA-p21, was regulated by p53 and contributed to apoptosis in mouse embryonic fibroblasts. However, the impact of such regulation on colorectal cancer (CRC) remains to be determined.
Total RNA was extracted from CRC cell lines and snap fresh frozen CRC samples from 2 CRC patient cohorts. The expression of lincRNA-p21 was quantified by quantitative real-time polymerase chain reaction analysis.
We discovered that the expression level of lincRNA-p21 was increased by elevated wild-type p53 induced by nutlin-3 in HCT-116 colon cancer cells. The expression level of lincRNA-p21 was significantly (P = .0208) lower in CRC tumor tissue when compared with the paired normal tissue from the same patient. There was no significant correlation of lincRNA-p21 with p53 status (wild-type vs. mutant). Tumors in the rectum showed a higher level of lincRNA-p21 than tumors in the colon (P = .00005). In addition, lincRNA-p21 in patients with stage III tumors was significantly higher than in those with stage I tumors (P = .007). Elevated levels of lincRNA-p21 were significantly associated with higher pT (P = .037 between pT 2 and 3) and vascular invasion (P = .017).
These results indicate that lincRNA-p21 may contribute to CRC disease progression.
长链非编码 RNA(lncRNA)已被证明是转录和转录后/翻译的新型调节剂。其中之一,lincRNA-p21,受 p53 调控,并促进小鼠胚胎成纤维细胞的凋亡。然而,这种调节对结直肠癌(CRC)的影响仍有待确定。
从 CRC 细胞系和 2 个 CRC 患者队列的新鲜冷冻 CRC 样本中提取总 RNA。通过定量实时聚合酶链反应分析定量 lincRNA-p21 的表达。
我们发现,在 HCT-116 结肠癌细胞中,升高的野生型 p53 诱导的 nutlin-3 增加了 lincRNA-p21 的表达水平。与同一患者的配对正常组织相比,CRC 肿瘤组织中 lincRNA-p21 的表达水平显著降低(P =.0208)。lincRNA-p21 与 p53 状态(野生型与突变型)之间无显著相关性。直肠肿瘤的 lincRNA-p21 水平高于结肠肿瘤(P =.00005)。此外,III 期肿瘤患者的 lincRNA-p21 水平明显高于 I 期肿瘤患者(P =.007)。升高的 lincRNA-p21 水平与更高的 pT(pT 2 与 3 之间的 P =.037)和血管侵犯(P =.017)显著相关。
这些结果表明 lincRNA-p21 可能有助于 CRC 疾病的进展。