Xia Jiangyan, Zhou Chenglin, Zhao Heng, Zhang Jun, Chai Xiaoming
Department of Anesthesiology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China.
Department of Anesthesiology, People's Hospital of Xuyi County, Xuyi, Huaian, Jiangsu, China.
Dig Dis Sci. 2025 Jan;70(1):215-232. doi: 10.1007/s10620-024-08756-4. Epub 2024 Dec 6.
Colorectal cancer (CRC) is an aggressive malignancy among malignant tumours, with a high incidence globally. LINC01614, a long non-coding RNA, has been identified as an essential regulator in multiple cancer types. However, its biological functions and underlying molecular mechanisms in CRC remain largely unknown.
In this study, we employed RT-qPCR to assess the expression levels of LINC01614 in CRC samples. In vitro, glucose metabolism experiments were conducted to evaluate glucose metabolism in cells. The binding relationship between miR-4443, PFKFB3, and LINC01614 was confirmed through fluorescence reporter gene detection. The subcellular localization of LINC01614 in CRC cells was determined using FISH and subcellular fractionation experiments. Additionally, a mouse subcutaneous tumor model was established for in vivo experiments.
Our findings reveal that LINC01614 is upregulated in CRC tissues. Silencing of LINC01614 suppresses the malignant behaviors of CRC cells, including cell proliferation, invasion, migration, and aerobic glycolysis. Furthermore, we discovered that LINC01614 promotes the expression of PFKFB3. Additional experiments demonstrated that LINC01614 binds to miR-4443, leading to the upregulation of PFKFB3 expression. Further experiments confirmed that the LINC01614/miR-4443/PFKFB3 axis promotes CRC cell malignancy by enhancing aerobic glycolysis. Additionally, we found that STAT1 promotes the transcription of LINC01614.
These findings uncover a novel regulatory pathway wherein STAT1-induced LINC01614 enhances PFKFB3 expression by sponging miR-4443, thereby accelerating CRC development. This understanding may lead to novel therapeutic strategies for CRC treatment.
结直肠癌（CRC）是恶性肿瘤中侵袭性较强的一种，在全球范围内发病率较高。LINC01614是一种长链非编码RNA，已被确定为多种癌症类型中的关键调节因子。然而，其在结直肠癌中的生物学功能和潜在分子机制在很大程度上仍不清楚。
在本研究中，我们采用RT-qPCR评估结直肠癌样本中LINC01614的表达水平。在体外，进行葡萄糖代谢实验以评估细胞中的葡萄糖代谢。通过荧光报告基因检测证实了miR-4443、PFKFB3和LINC01614之间的结合关系。使用FISH和亚细胞分级实验确定LINC01614在结直肠癌细胞中的亚细胞定位。此外，建立了小鼠皮下肿瘤模型用于体内实验。
我们的研究结果表明，LINC01614在结直肠癌组织中上调。沉默LINC01614可抑制结直肠癌细胞的恶性行为，包括细胞增殖、侵袭、迁移和有氧糖酵解。此外，我们发现LINC01614促进PFKFB3的表达。进一步的实验表明，LINC01614与miR-4443结合，导致PFKFB3表达上调。进一步的实验证实，LINC01614/miR-4443/PFKFB3轴通过增强有氧糖酵解促进结直肠癌细胞的恶性程度。此外，我们发现STAT1促进LINC01614的转录。
这些发现揭示了一种新的调控途径，即STAT1诱导的LINC01614通过海绵吸附miR-4443增强PFKFB3表达，从而加速结直肠癌的发展。这一认识可能会为结直肠癌的治疗带来新的治疗策略。
