Zhang Hong, Liu Xin, Zhang Wencheng, Deng Jiarong, Lin Chuxian, Qi Zhenhua, Li Yaqiong, Gu Yongqing, Wang Qi, Shen Liping, Wang Zhidong
Graduate Collaborative Training Base of Academy of Military Sciences, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, 100039, China.
Mol Biomed. 2023 Nov 1;4(1):37. doi: 10.1186/s43556-023-00147-x.
Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system, and represents a severe threat to the life and health of individuals. Increasing evidence supports the role of small nucleolar RNAs (snoRNAs) as critical regulatory gene in cancer development. Small Cajal body-specific RNAs (scaRNAs), a subtype of snoRNAs, are named for their subcellular localization within Cajal bodies. SCARNA12, which located at the intronic region of PHB2 in chromosome 12p13.31 with 270 nucleotides (nt) in length. It has been reported function as a diagnostic marker for cervical cancer. However, its biological functions and molecular mechanisms in CRC have yet to be elucidated. In this study, bioinformatics analysis revealed that SCARNA12 was highly expressed in CRC and positively correlated with poor prognosis in CRC patients. Additionally, SCARNA12 showed upregulated expression in CRC cell lines and clinical CRC tissue samples. Moreover, SCARNA12 overexpression in SW620 cells accelerated cell proliferation, suppressed the apoptosis rate, and enhanced tumorigenesis in vivo. The knockdown of SCARNA12 expression in HCT116 and HT29 cells resulted in contrasting effects. The functioning of SCARNA12 is mechanically independent of its host gene PHB2. Notably, the overexpression of SCARNA12 activated PI3K/AKT pathway in SW620 cells, and the malignancy degree of CRC cells was attenuated after treatment with MK2206 (a specific AKT inhibitor). Our findings demonstrated that SCARNA12 plays an oncogenic role in CRC progression and can be used as a potential diagnostic biomarker for CRC.
结直肠癌（CRC）是消化系统最常见的恶性肿瘤之一，对个体的生命和健康构成严重威胁。越来越多的证据支持小核仁RNA（snoRNAs）在癌症发展中作为关键调控基因的作用。小卡哈尔体特异性RNA（scaRNAs）是snoRNAs的一种亚型，因其在卡哈尔体内的亚细胞定位而得名。SCARNA12位于12号染色体p13.31上PHB2基因的内含子区域，长度为270个核苷酸（nt）。据报道，它可作为宫颈癌的诊断标志物。然而，其在结直肠癌中的生物学功能和分子机制尚未阐明。在本研究中，生物信息学分析显示SCARNA12在结直肠癌中高表达，且与结直肠癌患者的不良预后呈正相关。此外，SCARNA12在结直肠癌细胞系和临床结直肠癌组织样本中表达上调。此外，SW620细胞中SCARNA12的过表达加速了细胞增殖，抑制了凋亡率，并增强了体内肿瘤发生。HCT116和HT29细胞中SCARNA12表达的敲低产生了相反的效果。SCARNA12的功能在机制上独立于其宿主基因PHB2。值得注意的是，SCARNA12的过表达激活了SW620细胞中的PI3K/AKT通路，用MK2206（一种特异性AKT抑制剂）处理后，结直肠癌细胞的恶性程度减弱。我们的研究结果表明，SCARNA12在结直肠癌进展中起致癌作用，可作为结直肠癌潜在的诊断生物标志物。
