Overexpression of PTPRCAP inhibits biological function of lung adenocarcinoma through apoptosis pathway

PTPRCAP 过表达通过凋亡途径抑制肺腺癌的生物学功能。

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Abstract

BACKGROUND: PTPRCAP (protein tyrosine phosphatase receptor C-associated protein) has been implicated in tumor suppression in several malignancies; however, its role in lung adenocarcinoma (LUAD) remains unclear. This study aimed to investigate the expression profile and functional significance of PTPRCAP in LUAD. METHODS: Forty-five pairs of LUAD and adjacent non-tumor tissues were collected from patients undergoing surgery at Chengde Medical University Affiliated Hospital. PTPRCAP mRNA and protein levels were quantified by RT-qPCR and immunohistochemistry (IHC), respectively, and correlated with clinicopathological features. A549 and H1299 LUAD cell lines and BEAS-2B normal bronchial epithelial cells were used for in vitro assays. PTPRCAP was overexpressed via plasmid transfection (OE group) and compared with vector-transfected controls (Vector group). Functional assays included CCK-8 proliferation, scratch wound healing, Transwell migration/invasion, and Annexin V-PE apoptosis assays. Apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) were evaluated by Western blot. The effect of overexpression PTPRCAP on tumor growth was observed through nude mouse xenografts. RESULTS: PTPRCAP mRNA and protein levels were significantly lower in LUAD tissues than in adjacent non-tumor tissues (P < 0.05). Low PTPRCAP expression correlated with advanced TNM stage and poor differentiation (P < 0.05). In vitro, PTPRCAP expression was markedly reduced in A549 and H1299 cells compared with BEAS-2B. Overexpression of PTPRCAP significantly suppressed proliferation, migration, and invasion (P < 0.001), and increased apoptosis rates in both cell lines (P < 0.01). Mechanistically, PTPRCAP upregulation elevated pro-apoptotic Bax and cleaved caspase-3 while downregulating anti-apoptotic Bcl-2 (P < 0.05). In vivo xenograft experiments demonstrated that overexpression PTPRCAP inhibited tumor growth in nude mice (P < 0.001). CONCLUSIONS: PTPRCAP is downregulated in LUAD and acts as a tumor suppressor by promoting apoptosis and inhibiting proliferation, migration, and invasion. These findings suggest PTPRCAP as a potential therapeutic target for LUAD.

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