We identified the chr22-38_28785274–29,006,793.1–miR-106a-5p–DDHD1 axis from the CD4
+ T-cell related ceRNA network as a candidate for further analyses. The phospholipase A1 (PLA1) family members are classified as extracellular and intracellular and are implicated in different intracellular mechanisms. As a phosphatidic acid (PA)-preferring PLA1 (PA-PLA1), intracellular DDHD1 has been studied extensively owing to its implications for cancer development. DDHD1 is involved in the synthesis of lysophosphatidylinositol (LPI) [
32]. LPI activity is correlated with tumor growth and aggressiveness via its interaction with G protein-coupled receptor 55 (GPR-55) [
33‐
36]. Moreover, DDHD1 supports the proliferation and survival of colon cancer cells. Studies have also demonstrated that the inhibition of the MAPK/ERK and PI3K/Akt signaling pathways reduce the viability of colon cancer cells in vitro, and apoptotic cell death is increased by the silencing of DDHD1 via small interfering RNA [
37]. Our results were consistent with those of previous studies, which supported the effects of the lysophospholipid mediator DDHD1 on tumor processes. In neoplastic cells, by interacting with GPR-55, LPI induces ERK and the Akt signaling [
34]. MiR-106a-5p belongs to the miR-17 family. According to the consensus seed region, there are three clusters in the miR-17 family. MiR-106a-5p is located on Xq26.2, which belongs to the miR-106a-363 cluster. MiR-106a-5p is highly expressed in gastric [
38‐
42], breast [
43,
44], colorectal [
45], and non-small cell lung cancers [
46]. In squamous cell carcinomas [
47], colon cancers [
48], and gliomas [
49], miR-106a-5p is expressed at relatively low levels. Studies have also shown that in colorectal cancer, the inhibition of the anti-metastatic gene transforming growth factor-b receptor 2 (TGFBR2) increases cell migration and invasion via miR-106a-5p [
45]. In our study, DDHD1 was identified as a potential target of miR-106a-5p in colon cancer cells, which influences disease progression.
In our study, the chr22-38_28785274–29,006,793.1–miR-4319–GRHL1 axis from the CD8
+ T-cell related ceRNA network was identified as a candidate for further analyses. Grainyhead-like 1 (GRHL1) belongs to the GRHL transcription factor family, which comprises GRHL1, GRHL2, and GRHL3 [
50]. Studies have suggested that the Grainyhead family genes exhibit homologous DNA-binding immunoglobulin folding to the DNA-binding domain of the key tumor suppressor p53 and that these genes participate in wound healing, embryonic neural tube closure, and epidermal integrity [
51‐
53]. Recent studies have shown that these transcription factors are involved in various cancers, such as skin squamous cell carcinoma, gastric cancer, breast cancer, colorectal cancer, and cervical cancer [
54]. Moreover, GRHL2 knockdown in colorectal cancer cells inhibits cell proliferation by targeting ZEB1 [
55]. Huang et al. revealed that the expression of miR-4319 is inversely related to patient survival in colorectal cancer. Moreover, the overexpression of miR-4319 markedly reduces colorectal cancer cell proliferation by infecting ankyrin repeat and BTB domain-containing 1 (ABTB1) and alters the cell cycle distribution [
56]. Thus, we hypothesized that the chr22-38_28785274–29,006,793.1–miR-4319–GRHL1 axis is correlated with CD8
+ T cell functions and with the pathogenesis of colon cancer.