Ju Hui, Feng Yi, Mu Xiaojing, He Weitai, He Guifang, Tian Ben, Cai Duo, Liu Changchang, Song Yu, Chen Hao, Liu Shihai
Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266500, P.R. China.
Department of Rehabilitation, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266500, P.R. China.
Oncol Lett. 2025 Jul 24;30(4):459. doi: 10.3892/ol.2025.15205. eCollection 2025 Oct.
Gastric cancer (GC) is one of the most common malignancies globally, with notable morbidity and mortality rates. Despite advances in surgical techniques and adjuvant therapies, recurrence and metastasis remain major challenges, highlighting the need for novel biomarkers and therapeutic targets. Long non-coding RNAs (lncRNAs) have emerged as key regulators in various types of cancer, including GC, which can influence tumor progression through diverse mechanisms. LINC00467, in particular, has been implicated in non-small cell lung cancer, hepatocellular carcinoma and colorectal cancer, but the role of LINC00467 in GC remains poorly understood. The present study aimed to elucidate the role of LINC00467 in GC progression by investigating its expression patterns, functional impact on cellular behaviors and underlying molecular mechanisms. The expression levels of LINC00467 were evaluated in the GEPIA database of human gastric cancer samples, which demonstrated LINC00467 upregulation in 60 tumor tissue samples from patients with GC compared with that of paired para-cancerous control tissues. Functionally, LINC00467 promoted glycolysis in GC cells and enhanced their proliferative, migratory and invasive activities. From a mechanistic perspective, LINC00467 was able to bind to microRNA (miR)-141-3p in GC cells and a negative correlation between miR-141-3p and LINC00467 expression was observed in GC tissue samples. Inhibition of miR-141-3p partially reversed the effects of LINC00467 knockdown on GC cell malignancy and LINC00467 was further found to control the expression of the miR-141-3p target gene dihydropyriminidase-like 3 (DPYSL3) in GC cells. Furthermore, lactate accumulation from glycolysis activated the AKT signaling pathway to promote the transcriptional expression of LINC00467 in GC cells and led to persistent glycolysis and GC cell invasion. The present study findings suggested that LINC00467 potentially controls GC progression via regulation of the miR-141-3p/DPYSL3 pathway.
胃癌（GC）是全球最常见的恶性肿瘤之一，发病率和死亡率都很高。尽管手术技术和辅助治疗取得了进展，但复发和转移仍然是主要挑战，这凸显了对新型生物标志物和治疗靶点的需求。长链非编码RNA（lncRNAs）已成为包括GC在内的各种癌症的关键调节因子，其可通过多种机制影响肿瘤进展。特别是，LINC00467已被证明与非小细胞肺癌、肝细胞癌和结直肠癌有关，但LINC00467在GC中的作用仍知之甚少。本研究旨在通过研究LINC00467的表达模式、对细胞行为的功能影响及其潜在分子机制，阐明其在GC进展中的作用。在人胃癌样本的GEPIA数据库中评估了LINC00467的表达水平，结果显示与配对的癌旁对照组织相比，60例GC患者的肿瘤组织样本中LINC00467上调。在功能上，LINC00467促进GC细胞的糖酵解，并增强其增殖、迁移和侵袭活性。从机制角度来看，LINC00467能够与GC细胞中的微小RNA（miR）-141-3p结合，并且在GC组织样本中观察到miR-141-3p与LINC00467表达呈负相关。抑制miR-141-3p可部分逆转LINC00467敲低对GC细胞恶性程度的影响，并且进一步发现LINC00467可控制GC细胞中miR-141-3p靶基因二氢嘧啶酶样3（DPYSL3）的表达。此外，糖酵解产生的乳酸积累激活了AKT信号通路，以促进GC细胞中LINC00467的转录表达，并导致持续的糖酵解和GC细胞侵袭。本研究结果表明，LINC00467可能通过调节miR-141-3p/DPYSL3途径来控制GC进展。
