Huang Chaogang, Duan Ziqi, Chen Baojie, Xia Hailiang, Wang Guangxin
Department of General Surgery, Wuhan Third Hospital (Tongren Hospital of Wuhan University), China.
Department of General Surgery, Jianghan University, Wuhan, China.
Adv Clin Exp Med. 2025 Apr;34(4):623-632. doi: 10.17219/acem/188367.
The long non-coding RNA (lncRNA) LINC00969 is involved in human disease progression, and n6-methyladenosine (m6A) modification of lncRNAs in cancer has been proven to be a key regulatory mechanism. However, our understanding of its effects and mechanisms of action in papillary thyroid carcinoma (PTC) remains limited.
This study aimed to elucidate the role of methyltransferase-like 3 (METTL3)-induced m6A modification of LINC00969 in PTC tumorigenesis.
Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to analyze LINC00969 and METTL3 mRNA levels in PTC. The regulation of LINC00969 by METTL3 was confirmed using cell function experiments, molecular biology assays and bioinformatics analysis. LINC00969 stabilization analysis was performed to verify the regulatory roles of METTL3 and LINC00969.
LINC00969 expression was downregulated in PTC tissues. Increased LINC00969 expression inhibited the invasion, growth and migration of PTC cells. METTL3 downregulation in PTC mediated the m6A modification of LINC00969, increasing its stability. Furthermore, METTL3 levels were downregulated in PTC, and its silencing partially reversed the inhibitory effect of LINC00969 overexpression on PTC cell malignancy.
LINC00969 overexpression inhibits PTC cell malignancy via METTL3-mediated m6A modification. These findings suggest that METTL3-m6A-LINC00969 is a promising therapeutic target for PTC.
长链非编码RNA（lncRNA）LINC00969参与人类疾病进展，且lncRNAs的N6-甲基腺苷（m6A）修饰在癌症中已被证明是一种关键调控机制。然而，我们对其在甲状腺乳头状癌（PTC）中的作用及作用机制的了解仍然有限。
本研究旨在阐明甲基转移酶样3（METTL3）诱导的LINC00969的m6A修饰在PTC肿瘤发生中的作用。
采用定量逆转录聚合酶链反应（qRT-PCR）分析PTC中LINC00969和METTL3 mRNA水平。通过细胞功能实验、分子生物学分析和生物信息学分析证实METTL3对LINC00969的调控作用。进行LINC00969稳定性分析以验证METTL3和LINC00969的调控作用。
PTC组织中LINC00969表达下调。LINC00969表达增加抑制了PTC细胞的侵袭、生长和迁移。PTC中METTL3下调介导了LINC00969的m6A修饰，增加了其稳定性。此外，PTC中METTL3水平下调，其沉默部分逆转了LINC00969过表达对PTC细胞恶性程度的抑制作用。
LINC00969过表达通过METTL3介导的m6A修饰抑制PTC细胞恶性程度。这些发现表明METTL3-m6A-LINC00969是PTC一个有前景的治疗靶点。
