Cao Qifeng, Yang Weiqin, Ji Xili, Wang Wei
Department of Respiratory Medicine, Taizhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenling, China.
Department of Gastroenterology, Taizhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenling, China.
Front Genet. 2020 Dec 8;11:597795. doi: 10.3389/fgene.2020.597795. eCollection 2020.
Emerging evidence suggests that long non-coding RNA (lncRNA) plays a critical role in human disease progression. Recently, a novel lncRNA ST8SIA6-AS1 was shown as an important driver in various cancer types. Nevertheless, its contribution to lung adenocarcinoma (LUAD) remains undocumented. Herein, we found that ST8SIA6-AS1 was frequently overexpressed in LUAD cell lines, tissues, and plasma. Depletion of ST8SIA6-AS1 significantly inhibited LUAD cell proliferation and invasion and tumor growth . In term of mechanism, ST8SIA6-AS1 was transcriptionally repressed by tumor suppressor p53, and ST8SIA6-AS1 was mainly located in the cytoplasm and could abundantly sponge miR-125a-3p to increase nicotinamide N-methyltransferase (NNMT) expression, thereby facilitating LUAD malignant progression. Clinically, high ST8SIA6-AS1 was positively correlated with larger tumor size, lymph node metastasis, and later TNM stage. Moreover, ST8SIA6-AS1 was identified as an excellent indicator for MM diagnosis and prognosis. Collectively, our data demonstrate that ST8SIA6-AS1 is a carcinogenic lncRNA in LUAD, and targeting the axis of ST8SIA6-AS1/miR-125a-3p/NNMT may be a promising treatment for LUAD patients.
新出现的证据表明,长链非编码RNA(lncRNA)在人类疾病进展中起关键作用。最近,一种新型lncRNA ST8SIA6-AS1被证明是多种癌症类型的重要驱动因素。然而,其对肺腺癌(LUAD)的作用仍未得到证实。在此,我们发现ST8SIA6-AS1在LUAD细胞系、组织和血浆中经常过度表达。ST8SIA6-AS1的缺失显著抑制了LUAD细胞的增殖、侵袭和肿瘤生长。在机制方面,肿瘤抑制因子p53转录抑制ST8SIA6-AS1,且ST8SIA6-AS1主要位于细胞质中,可大量吸附miR-125a-3p以增加烟酰胺N-甲基转移酶(NNMT)的表达,从而促进LUAD的恶性进展。临床上,高表达的ST8SIA6-AS1与更大的肿瘤大小、淋巴结转移和更晚的TNM分期呈正相关。此外,ST8SIA6-AS1被确定为LUAD诊断和预后的优秀指标。总体而言,我们的数据表明ST8SIA6-AS1是LUAD中的致癌lncRNA,靶向ST8SIA6-AS1/miR-125a-3p/NNMT轴可能是LUAD患者一种有前景的治疗方法。