Abstract
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.
Highlights
Hepatocellular carcinoma (HCC, LIHC) is the most common type of primary liver cancer, ranking sixth for incidence and fourth for mortality (Bray et al, 2018)
The interactors of peptidylprolyl isomerase A (PPIA) were obtained from BioGRID
We found that overexpression of peptidylprolyl isomerase A pseudogene 22 (PPIAP22) in MHCC-97H cells resulted in decreased expression of miR-197-3p (Figure 4F; p < 0.05) and increased expression of PPIA (Figure 4G; p < 0.001)
Summary
Hepatocellular carcinoma (HCC, LIHC) is the most common type of primary liver cancer, ranking sixth for incidence and fourth for mortality (Bray et al, 2018). In contrast to many other diseases, the overall burden of HCC worldwide is increasing over time. Due to the frequent recurrence, intrahepatic metastasis of HCC, and the shortage of effective treatments, Role of PPIAP22 in HCC the prognosis of HCC is not optimistic (Wang et al, 2019; Yang et al, 2019). The underlying molecular mechanism of HCC development is still under exploration. More and more evidence suggests that the dysregulation of non-coding RNAs (ncRNAs) plays an essential role in HCC during the past few decades. By affecting the signal transduction pathways in cancer cells and the interaction between cancer cells and the microenvironment, ncRNAs mediate HCC development and progression (Pea et al, 2020)
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