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Tumor Discovery PTMAP5–hsa-miR-22-3p–KIF2C axis in HCC development

data, primarily relying on pertinent information derived Subsequently, lncRNAs that may bind to hsa-miR-22-3p
from the TCGA database. On the other hand, the GEPIA were predicted using the miRNet and StarBase databases.
web server acts as a valuable resource for scrutinizing In StarBase, 116 upstream lncRNAs were identified, and
gene expression patterns in both tumor and normal in miRNet, 52 upstream lncRNAs were found. Cross-
samples, drawing from the TCGA and GTEx databases. By referencing the two databases resulted in the identification
conducting a Venn analysis of the two sets of co-expressed of a total of 50 lncRNAs, including DNAJC27-AS1,
genes, we identified genes that were co-expressed with LINC02012, LINC00997, RGMB-AS1, PAX8-AS1,
KIF2C, which increased the reliability of the results. CRYZL2P-SEC16B, GABPB1-AS1, SNHG16, STAG3L5P-
Further, enrichment analysis of these co-expressed genes PVRIG2P-PILRB, NEAT1, LINC00858, LINC01184,
demonstrated significant involvement in pathways related AGAP1-IT1, LINC01278, NORAD, LINC02381, NKILA,
to the actin cytoskeleton. The actin cytoskeleton plays a LINC00482, ADORA2A-AS1, MALAT1, LINC00630,
pivotal role in cancer spread and metastasis, indicating TBX2-AS1, OIP5-AS1, TBC1D3P1-DHX40P1, HCP5,
a close association between these genes and cancer H19, ZSCAN16-AS1, LINC00963, MEG3, CD27-AS1,
progression. 46,47 Therefore, the hsa-miR-22-3P–KIF2C ADIRF-AS1, RBPMS-AS1, PSMB8-AS1, TRPM2-AS,
pathway may regulate the actin cytoskeleton, potentially SLC9A3-AS1, FTX, MIR4435-2HG, THAP7-AS1, and
50
inhibiting invasion and metastasis in HCC, and thereby LOXL1-AS1. In a study by Hu et al., LINC00858 was
halting the advancement of the disease. found to be notably upregulated in HCC tumor tissues
compared to normal samples, suggesting a potential
NcRNAs, including pseudogenes and lncRNAs, are association between LINC00858 and the development and
significant players in gene regulation. They can function as advancement of HCC.
ceRNAs, interacting with mRNAs to compete for miRNA
binding. Studies suggest that lncRNAs are instrumental To summarize, the upregulated expression of lncRNAs
in the regulation of tumorigenesis and tumor growth, and pseudogenes results in the suppression of hsa-miR-
influencing cellular processes such as proliferation, 22-3p, which in turn elevates KIF2C expression. This
differentiation, stress response, cellular aging, and dysregulation affects the actin cytoskeleton and contributes
programmed cell death (apoptosis). Earlier research to the advancement of HCC.
48
has indicated a strong correlation between the irregular Numerous studies have provided evidence to support
expression of lncRNAs and the emergence, growth, and the notion that the presence of immune cells within tumors
metastasis of gastric cancer. 49 can influence the effectiveness and prognosis of various
treatment modalities, such as chemotherapy, radiotherapy,
To further investigate these regulatory interactions, we 51-53
utilized StarBase to predict upstream pseudogenes that and immunotherapy. Our investigation uncovered a
significant positive association between KIF2C expression
could potentially interact with the hsa-miR-22-3P–KIF2C and the infiltration of multiple immune cell types in
axis, identifying 271 pseudogenes. In our pursuit to identify HCC. Furthermore, our observations revealed a direct
microRNA targets, we leveraged extensive CLIP-seq and correlation between KIF2C and biomarkers linked to
degradome experimental datasets, providing a variety of these infiltrating immune cells. These findings suggest that
visual platforms for the exploration of microRNA-target immune cell infiltration in the tumor microenvironment
interactions. These resources offer abundant data on may partially contribute to the oncogenic effects mediated
interactions between miRNA and ncRNA, miRNA and by KIF2C in HCC.
mRNA, RNA-binding protein (RBP) and RNA, as well as
RNA-RNA interactions. Among the liver specimens, five To maximize the effectiveness of immunotherapy, it is
pseudogenes (EIF5AP4, PTMAP5, RPL14P1, RPL37P6, crucial to ensure adequate immune cell presence within
and SPCS2P4) were significantly upregulated compared the tumor microenvironment and appropriate engagement
to the normal control group. Correlation analysis revealed of immune checkpoints. In light of this, we carried out an
that PTMAP5, RPL14P1, and SPCS2P4 were negatively analysis to explore the relationship between KIF2C and key
correlated with hsa-miR-26b5p. Based on the ceRNA regulatory immune checkpoints. Our results demonstrate
hypothesis, a new PTMAP5–hsa-miR-22-3P–KIF2C a significant link between elevated KIF2C expression and
regulatory network was constructed, with an alternative the immune checkpoints PD1, PD-L1, and CTLA-4 in
network involving RPL14P1/SPCS2P4–hsa-miR-22-3P– HCC. This finding implies that targeting KIF2C could
KIF2C. This network demonstrated that the heightened potentially enhance the efficacy and prognostic value of
expression of lncRNAs/pseudogenes led to the reduced immunotherapeutic approaches for HCC.
expression of hsa-miR-22-3, which in turn increased While the precise role and molecular mechanisms of
KIF2C expression, contributing to HCC progression. the PTMAP5–hsa-miR-22-3p–KIF2C regulatory pathway

Volume 3 Issue 3 (2024) 20 doi: 10.36922/td.2846