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C-Myb facilitates immune escape of esophageal adenocarcinoma cells through the miR-145-5p/SPOP/PD-L1 axis.


ABSTRACT: Esophageal adenocarcinoma (EAC), a subtype of esophageal carcinoma, is a severe health problem associated with high death rate and poor prognosis. Immunotherapy has proven to be effective in many solid tumors, including EAC, but immune escape blocks its effectiveness. Thus, we explored the mechanisms and functional role of c-Myb in immune escape of EAC cells. Clinical EAC tissues were collected for determining the expression of c-Myb, speckled POZ protein (SPOP), and miR-145-5p. Functional assays were then performed to detect the interactions between c-Myb and SPOP as well as between SPOP and miR-145-5p. EAC cell invasion and migration were assessed. Next, T cells were sorted and cocultured with EAC cells with different treatments followed by detection of T-cell viability. In addition, a mouse model of EAC was constructed for relevant in vivo assays. c-Myb and miR-145-5p were highly expressed and SPOP had low expressions in EAC. c-Myb activated the transcription of miR-145-5p, which in turn targeted SPOP. Further, SPOP accelerated the ubiquitination of PD-L1 to enhance its expression. Overexpression of PD-L1 suppressed T-cell functions and promoted proliferative and migrative abilities of EAC cells to induce immune escape. The above findings were also confirmed in the ECA mouse model in vivo. Our findings uncovered that c-Myb can promote the immune escape of EAC cells by favoring the transcription of miR-145-5p and inhibiting SPOP-dependent ubiquitination and degradation of PD-L1, thus, presenting new target for EAC adjunct therapy.

SUBMITTER: Zhang L 

PROVIDER: S-EPMC8473478 | biostudies-literature |

REPOSITORIES: biostudies-literature

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