Zhang Xiao, Zhao Tingyu, Wu Cheng, Shen Hengyang, Yi Jianing, Liu Lingxiang
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, No.300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
BMC Cancer. 2025 May 6;25(1):829. doi: 10.1186/s12885-025-14170-4.
It has been reported that lncRNA CASC19 is abnormally highly expressed in colorectal cancer (CRC) progression, suggesting that it may regulate the occurrence and metastasis of CRC, but its specific mechanism is still unclear. To further explore the effect of CASC19 on CRC, we overexpressed or knocked down CASC19 in HR4838 cells. The results of Transwell invasion assay and cell clonogenic assay showed that CASC19 promoted cell invasion and proliferation. Flow cytometry results showed that CASC19 inhibited cell apoptosis. In addition, by detecting glucose uptake, lactate content and ATP production, it was found that CASC19 promoted glycolysis, while CASC19 silencing had the opposite effect. Interestingly, small nuclear ribonucleoprotein polypeptide A (SNRPA) is an RNA binding protein of CASC19. Overexpression of SNRPA promoted tumor cell invasion, proliferation, glycolysis, and inhibits apoptosis, while SNRPA silencing has the opposite effect. Moreover, SNRPA overexpression reversed the inhibitory effect of CASC19-sh on invasion, proliferation and glycolysis of HR4838 cells and the promoting effect on apoptosis, which was mediated by activating the Wnt/β-catenin pathway. In the subcutaneous transplantation tumor model of BALB/c nude mice, we observed that the tumor growth of CASC19 knockdown mice was slower, and the tumor weight and volume were smaller, which was related to the low expression of CASC19 and SNRPA. In conclusion, our results showed that CASC19 promoted the growth and glycolysis of CRC cells and tumor metastasis in mice by upregulating SNRPA, which may provide a new molecular marker for the diagnosis and treatment of CRC.
据报道，lncRNA CASC19在结直肠癌（CRC）进展过程中异常高表达，提示其可能调控CRC的发生和转移，但其具体机制仍不清楚。为进一步探究CASC19对CRC的影响，我们在HR4838细胞中过表达或敲低CASC19。Transwell侵袭实验和细胞克隆形成实验结果显示，CASC19促进细胞侵袭和增殖。流式细胞术结果显示，CASC19抑制细胞凋亡。此外，通过检测葡萄糖摄取、乳酸含量和ATP生成，发现CASC19促进糖酵解，而沉默CASC19则产生相反的效果。有趣的是，小核核糖核蛋白多肽A（SNRPA）是CASC19的一种RNA结合蛋白。过表达SNRPA可促进肿瘤细胞侵袭、增殖、糖酵解并抑制凋亡，而沉默SNRPA则产生相反的效果。此外，SNRPA过表达可逆转CASC19-sh对HR4838细胞侵袭、增殖和糖酵解的抑制作用以及对凋亡的促进作用，这是通过激活Wnt/β-连环蛋白通路介导的。在BALB/c裸鼠皮下移植瘤模型中，我们观察到敲低CASC19的小鼠肿瘤生长较慢，肿瘤重量和体积较小，这与CASC19和SNRPA的低表达有关。总之，我们的结果表明，CASC19通过上调SNRPA促进CRC细胞生长、糖酵解及小鼠肿瘤转移，这可能为CRC的诊断和治疗提供新的分子标志物。
