lncRNA LINC02323 predicts adverse neoadjuvant chemotherapy outcomes of gastric cancer patients and regulates cell sensitivity to 5-fluorouracil by negatively modulating miR-139-3p

lncRNA LINC02323 可预测胃癌患者新辅助化疗的不良预后,并通过负调控 miR-139-3p 来调节细胞对 5-氟尿嘧啶的敏感性。

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Abstract

BACKGROUND/OBJECTIVE: Drug resistance is a challenging problem in the clinical chemotherapy of gastric cancer. Identification of predictive biomarkers for chemotherapy outcomes could improve therapeutic efficacy and patient prognosis. This study aimed to assess the significance of long non-coding RNA (lncRNA) LINC02323 in gastric cancer progression and neoadjuvant chemotherapy and to explore its potential regulatory mechanism. MATERIALS AND METHODS: This study enrolled 117 patients with gastric cancer who received neoadjuvant chemotherapy combined with surgical treatment and 35 patients with benign gastroscopic results. The expression of LINC02323 in gastric mucosal tissues of study subjects was analyzed by PCR, and its association with chemotherapy efficacy and cancer development was evaluated. Gastric cancer cells were treated with 5-FU, and the effect of LINC02323 on cell growth and motility under 5-FU treatments was evaluated using CCK8 and transwell assays. RESULTS: LINC02323 was upregulated in gastric cancer patients, which was related to advanced T stage, occurrence of lymph node metastasis, and less pathological response to chemotherapy. LINC02323 serves as a prognostic biomarker for predicting poor overall survival of gastric cancer patients receiving neoadjuvant chemotherapy. Silencing LINC02323 suppressed the proliferation and motility of gastric cancer cells treated with 5-FU and induced cell apoptosis, indicating the enhanced sensitivity of gastric cancer cells to 5-FU. miR-139-3p was negatively regulated by LINC02323 and could reverse the function of LINC02323 in 5-FU-treated gastric cancer cells. CONCLUSION: Upregulated LINC02323 expression in gastric cancer is associated with malignant progression, adverse prognosis, and chemotherapy resistance. Silencing LINC02323 could enhance the sensitivity of gastric cancer cells to 5-FU by negatively modulating miR-139-3p expression.

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