International Journal of Clinical Research

Objective To investigate the expression of LAPTM4B in renal cell carcinoma (RCC) and the mechanism by which it activates the PI3K/AKT signaling pathway to promote tumor malignancy and proliferation. Methods Sixty-four pairs of tumor tissue and adjacent normal tissue samples from RCC patients who underwent radical nephrectomy in our hospital from June 2019 to June 2023 were collected. The expression level of LAPTM4B was detected by immunohistochemical staining, Western blot, and fluorescence quantitative PCR. A 786-O cell line with continuous down-regulation of LAPTM4B was established. The cell proliferation and its cycle changes were analyzed by CCK-8 assay, colony formation assay, and flow cytometry. The phosphorylation status of the main proteins of the PI3K/AKT signaling pathway was detected by Western blot. Rescue experiments with the PI3K activator 740Y-P were conducted to explore whether LAPTM4B affects the growth of renal cell carcinoma through the PI3K-AKT pathway. Results The expression level of LAPTM4B in renal cancer tissues was significantly higher than that in adjacent normal renal tissues (P < 0.001). Moreover, the higher expression level was also closely related to the clinical stage, Fuhrman grade, and lymph node metastasis of the tumor (P < 0.05). After knockdown of LAPTM4B, the growth vitality of 786-O cells was significantly weakened, the G1 phase was delayed, and the levels of p-PI3K and p-AKT proteins were simultaneously reduced. After adding 740Y-P, this inhibitory effect was alleviated, further confirming that LAPTM4B promotes the malignant proliferation of renal cell carcinoma cells by activating the PI3K/AKT signaling network. Conclusion LAPTM4B is highly overexpressed in renal cell carcinoma, and its activation of the PI3K/AKT signaling pathway leads to malignant proliferation of cancer cells, presenting a prospect as a target drug for renal cell carcinoma treatment.

Renal cell carcinoma; LAPTM4B; PI3K/AKT signaling pathway; Malignant proliferation