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The expression of long noncoding RNA CRCAL‐3 in colorectal cancer and its impacts on cell proliferation and migration

机译:结直肠癌中长的非分量RNA CRCAL-3的表达及其对细胞增殖和迁移的影响

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Abstract Long noncoding RNAs (lncRNAs) have been implicated in colorectal cancer (CRC). And lncRNA RP11‐138J23.1 (CRCAL‐3) was previously reported as a candidate regulator of CRC development. But its regulating functions have not been fully elucidated. Here, we analyzed RNA sequencing data from the Cancer Genome Atlas (TCGA) and 253 CRC patients treated in our hospital to assess expression dysregulation of CRCAL‐3, and the correlation between CRCAL‐3 expression and disease progression. Further, polymerase chain reaction (PCR) assay on different cell lines and knockdown experiments by small interfering RNA were performed to assess functions of CRCAL‐3 in proliferation and migration of CRC cells. As a result, analyses on TCGA datasets showed an upregulated CRCAL‐3 expression in 14 solid tumors, including CRC. PCR assay on 253 cases of CRC tissue and 114 cases of normal adjacent tissue confirmed this expression upregulation. Also, CRCAL‐3 expression was exhibited by survival analyses on the 253 CRC patients, to have a negative correlation with patients' overall and progression‐free survivals. PCR assay on different cell lines showed that CRC cells expressed a higher level of CRCAL‐3, compared with normal colonic epithelial cells. In vitro knockdown of CRCAL‐3 resulted in an obvious retardation of proliferation and migration in two CRC cell lines (HCT116 and DLD‐1). Moreover, CRCAL‐3 knockdown was observed in xenograft models to repress cell proliferation and enhance cisplatin sensitivity. Taking these results together, CRCAL‐3 emerged as a biomarker for early diagnosis, prognosis prediction, and individualized treatment of CRC.
机译:摘要长度非划分RNA(LNCRNA)涉及结直肠癌(CRC)。和LNCRNA RP11-138J23.1(CRCAL-3)先前被报告为CRC发育的候选监管机构。但其调节功能尚未完全阐明。在这里,我们分析了来自癌症基因组Atlas(TCGA)和253名CRC患者的RNA测序数据,并在医院治疗的253名CRC患者评估CRCAL-3的表达失调,以及CRCAL-3表达和疾病进展之间的相关性。此外,通过小干扰RNA在不同细胞系上的聚合酶链反应(PCR)测定和小干扰RNA的敲低实验,以评估CRCAL-3在CRC细胞的增殖和迁移中的功能。结果,TCGA数据集的分析显示了14个实体瘤中的上调CRCAL-3表达,包括CRC。 PCR测定在253例CRC组织和114例正常相邻组织的情况下证实了这种表达上调。此外,通过对253例CRC患者的存活分析表现出CRCAL-3表达,与患者的总体和无进展幸存保持不相关。与正常结肠上皮细胞相比,不同细胞系上的PCR测定表明CRC细胞表达了更高水平的CRCAL-3。体外敲低CRCAL-3导致两种CRC细胞系(HCT116和DLD-1)中的增殖和迁移明显延迟。此外,在异种移植模型中观察到CRCAL-3敲低,以抑制细胞增殖并增强顺铂敏感性。将这些结果一起服用,CRCAL-3作为早期诊断,预后预测和CRC的个体化治疗的生物标志物。

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