PDRG1 predicts a poor prognosis and facilitates the proliferation and metastasis of colorectal cancer

被引:3
|
作者
Xu, Yixin [1 ,2 ,3 ]
Liu, Jia [4 ]
Jiang, Tao [2 ,3 ]
Shi, Linsen [2 ,3 ]
Shang, Liang [1 ,5 ]
Song, Jun [2 ,3 ]
Li, Leping [1 ,5 ]
机构
[1] Shandong Univ, Cheeloo Coll Med, Shandong Prov Hosp, Dept Gastroenterol Surg, Jinan 250021, Shandong, Peoples R China
[2] Xuzhou Med Univ, Affiliated Hosp, Dept Gen Surg, Xuzhou, Jiangsu, Peoples R China
[3] Xuzhou Med Univ, Inst Digest Dis, Xuzhou, Jiangsu, Peoples R China
[4] Xuzhou Med Univ, Affiliated Hosp, Dept Pathol, Xuzhou, Jiangsu, Peoples R China
[5] Shandong Prov Hosp, Engn Lab, Dept Digest Tumor Translat Med, Jinan 250021, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
CRC; PDRG1; Proliferation; Metastasis; CELL-CYCLE; TRANSCRIPTIONAL REGULATION; P53; P21; GENE; EXPRESSION; INDUCTION; INHIBITION; APOPTOSIS; CDKN1A;
D O I
10.1016/j.yexcr.2021.112924
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objective: The incidence and mortality of colorectal cancer (CRC) is increasing yearly and CRC patients are becoming younger in global. Evidences have revealed the carcinogenic effect of p53 and DNA damage-regulated gene 1 (PDRG1) in several types of tumors. However, its biological function is yet to be investigated in CRC. This study aimed to unveil the prooncogenic role of PDRG1 in CRC. Methods: We detected the expression and clinical pathological features of PDRG1 in CRC tissues and paired nontumor adjacent tissues. The biological role and molecular mechanism of PDRG1 in CRC were characterized through a range of in vitro and in vivo experiments and datasets analysis. Result: We identified the significant up-regulated expression of PDRG1 both in CRC tissues and cell, and higher expression of PDRG1 was associated with worse clinicopathological stage and poorer survival outcome. Cox regression analysis revealed that PDRG1 is an independent prognostic factor for CRC patients. Silencing of PDRG1 significantly retarded CRC cell vitality, invasion and migration, induced cell apoptosis and G0/G1 phase arrest. PDRG1 knockdown also attenuated tumor growth and metastasis as evidencing in vivo experiment. The expression of p21 and apoptosis related protein was enhanced with the knockdown of PDRG1 while cell cycle protein was inhibited. Conclusion: PDRG1 function as a novel oncogene and participate in malignant progression of CRC by regulating p21-mediated signal pathway, suggesting that it can serve as a valuable predictive biomarker for diagnosing of CRC patient and a promising target for therapy.
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页数:12
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