A Critical Role of Peptidylprolyl Isomerase A Pseudogene 22/microRNA-197-3p/Peptidylprolyl Isomerase A Axis in Hepatocellular Carcinoma

被引:13
作者
Gu, Yuwei [1 ]
Wang, Chao [2 ]
Chen, Shengsen [3 ,4 ]
Tang, Jia [1 ]
Guo, Xiaoxiao [1 ]
Hu, Wei [5 ]
Cui, An [1 ]
Zhang, Dian [2 ]
Yu, Kangkang [1 ]
Chen, Mingquan [1 ,2 ]
机构
[1] Huashan Hosp, Dept Infect Dis, Shanghai, Peoples R China
[2] Huashan Hosp, Emergency Dept, Shanghai, Peoples R China
[3] Univ Chinese Acad Sci, Canc Hosp, Dept Endoscopy, Zhejiang Canc Hosp, Hangzhou, Peoples R China
[4] Chinese Acad Sci, Inst Canc & Basic Med IBMC, Hangzhou, Peoples R China
[5] Fudan Univ, Shanghai Med Coll, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
hepatocellular carcinoma; pseudogene; PPIA; chemokine; macrophage; LONG NONCODING RNAS; CANCER; CYCLOPHILIN; MYC; MICROENVIRONMENT; IDENTIFICATION; IMMUNOTHERAPY; CHEMOKINES; MECHANISM; PROTEINS;
D O I
10.3389/fgene.2021.604461
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The burden of hepatocellular carcinoma (HCC) worldwide is increasing over time, while the underlying molecular mechanism of HCC development is still under exploration. Pseudogenes are classified as a special type of long non-coding RNAs (lncRNAs), and they played a vital role in regulating tumor-associated gene expression. Here, we report that a pseudogene peptidylprolyl isomerase A pseudogene 22 (PPIAP22) and its parental gene peptidylprolyl isomerase A (PPIA) were upregulated in HCC and were associated with the clinical outcomes of HCC. Further investigation revealed that PPIAP22 might upregulate the expression of PPIA through sponging microRNA (miR)-197-3p, behaving as competing endogenous RNA (ceRNA). PPIA could participate in the development of HCC by regulating mRNA metabolic process and tumor immunity based on the functional enrichment analysis. We also found a strong correlation between the expression levels of PPIA and the immune cell infiltration or the expression of chemokines, especially macrophage, C-C motif chemokine ligand 15 (CCL15), and C-X-C motif chemokine ligand 12 (CXCL12). Our findings demonstrate that the PPIAP22/miR-197-3p/PPIA axis plays a vital role in the progression of HCC by increasing the malignancy of tumor cells and regulating the immune cell infiltration, especially macrophage, through CCL15-CCR1 or CXCL12-CXCR4/CXCR7 pathways.
引用
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页数:15
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