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

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. 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. 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. 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.胃癌临床化疗中，耐药性是一项极具挑战性的难题。筛选化疗疗效的预测生物标志物，有助于提升治疗效果并改善患者预后。本研究旨在评估长链非编码RNA（long non-coding RNA，lncRNA）LINC02323在胃癌进展及新辅助化疗中的作用，并探讨其潜在调控机制。本研究纳入117例接受新辅助化疗联合手术治疗的胃癌患者，以及35例胃镜检查结果为良性的受试者。采用聚合酶链式反应（Polymerase Chain Reaction，PCR）检测受试者胃黏膜组织中LINC02323的表达水平，并评估其与化疗疗效及癌症发生发展的相关性。采用5-氟尿嘧啶（5-Fluorouracil，5-FU）处理胃癌细胞，通过细胞计数试剂盒-8（Cell Counting Kit-8，CCK-8）及Transwell小室实验，评估LINC02323对5-FU处理下胃癌细胞生长及运动能力的影响。胃癌患者组织中LINC02323呈高表达，且与较高的T分期、淋巴结转移发生及较差的化疗病理应答反应相关。LINC02323可作为预测接受新辅助化疗的胃癌患者不良总生存期的预后生物标志物。沉默LINC02323可抑制5-FU处理下胃癌细胞的增殖与运动能力，并诱导细胞凋亡，提示胃癌细胞对5-FU的敏感性得以增强。miR-139-3p受LINC02323负向调控，且可逆转LINC02323在5-FU处理的胃癌细胞中的功能。胃癌组织中LINC02323的高表达与恶性进展、不良预后及化疗耐药性相关。沉默LINC02323可通过负向调控miR-139-3p的表达，增强胃癌细胞对5-FU的敏感性。