CCR4a promotes metastasis and invasion of ovarian cancer by downregulating LRRC4 via PI3K/AKT Signaling Pathway Activation

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Abstract

Background It has been established that CCR4-NOT transcription complex subunit 6 (CCR4a) can promote the growth of some malignancies. Its role and clinical significance in ovarian cancer, however, have not been documented. This article examined the spread of cancer following CCR4a modulation. Methods Bioinformatics was used to analyze the prognosis of CCR4a using the KM plot dataset. The CCR4a protein was identified by immunohistochemistry investigation in ovarian cancer tissues. Cellular responses were noted following both up-and-down-regulation of CCR4a. The mechanism was validated using Western blotting and RNA sequencing. Results Ovarian cancer metastases were positively correlated with CCR4a expression, and a shorter survival period was linked to higher expression. In contrast, down-regulation of CCR4a inhibits LRRC4 (leucine-rich repeat containing 4), which in turn activates the PI3K/AKT signaling pathway, which in turn promotes cell invasion and migration. In vivo, CCR4a up-regulation increased carcinogenic potential while down-regulation reduced it. Conclusions In ovarian cancer tissues, high CCR4a expression suggested reduced survival. In ovarian cancer cells, CCR4a facilitated migration and invasion by downregulating LRRC4 through the stimulation of PI3K/AKT signaling. It may be a useful target for prognostic and diagnostic purposes.

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