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

Ann Med. 2024 Dec;56(1):2424513. doi: 10.1080/07853890.2024.2424513. Epub 2024 Nov 7.

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.

Keywords: Gastric cancer; cell growth; invasion; migration; neoadjuvant chemotherapy; prognosis.

MeSH terms

  • Aged
  • Antimetabolites, Antineoplastic / pharmacology
  • Antimetabolites, Antineoplastic / therapeutic use
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation* / drug effects
  • Drug Resistance, Neoplasm* / genetics
  • Female
  • Fluorouracil* / pharmacology
  • Fluorouracil* / therapeutic use
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Neoadjuvant Therapy* / methods
  • Prognosis
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / pathology
  • Up-Regulation

Substances

  • Fluorouracil
  • RNA, Long Noncoding
  • MicroRNAs
  • MIRN139 microRNA, human
  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor

Grants and funding

This study was funded by Shanghai Pudong New Area People’s Hospital Qihang Plan Talent Cultivation Project (PRYQH202405).