目的:探讨circRNA调控因子MBNL1和QKI在食管鳞状细胞癌进展中的作用。
背景:MBNL1和QKI是pre-mRNA选择性剪接的关键调节因子,对于控制circRNA产生至关重要-一种新兴的生物标志物和肿瘤进展的功能调节因子。尽管他们公认的角色,他们参与ESCC进展仍有待探索.
方法:使用来自GEO数据库的数据,在ESCC和邻近正常组织的28个组织对中检测了MBNL1和QKI的表达水平。此外,共151个ESCC组织样本,从T1阶段到T4阶段,每个阶段包括13、43、87和8例,分别,用于免疫组织化学(IHC)分析。RNA测序用于检查circRNAs的表达谱,lncRNAs,和3个正常组织的mRNA,3ESCC组织,野生型(WT)和具有MBNL1或QKI敲除的3对KYSE150细胞。Transwell,菌落形成,和皮下肿瘤发生测定评估MBNL1或QKI敲除对ESCC细胞迁移的影响,入侵,和扩散。
结果:ESCC发病显著改变了MBNL1和QKI的表达水平,影响不同的RNA物种。MBNL1或QKI表达升高与患者年龄或肿瘤浸润深度相关,分别。MBNL1或QKI敲除显着增强癌细胞迁移,入侵,扩散,和肿瘤生长。此外,MBNL1或QKI的缺失调节了多种circRNAs的表达谱,在许多lncRNAs和mRNAs的表达中引起广泛的下游改变。虽然在前20个差异表达基因中circRNA和lncRNA的功能仍不清楚,据报道,SLCO4C1、TMPRSS15和MAGEB2等mRNA与肿瘤进展有关。
结论:本研究强调了MBNL1和QKI在ESCC中的肿瘤抑制作用,提出它们作为ESCC诊断和治疗的潜在生物标志物和治疗靶点。
OBJECTIVE: To investigate the role of circRNA regulators MBNL1 and
QKI in the progression of esophageal squamous cell carcinoma.
BACKGROUND: MBNL1 and
QKI are pivotal regulators of pre-mRNA alternative splicing, crucial for controlling circRNA production - an emerging biomarker and functional regulator of tumor progression. Despite their recognized roles, their involvement in ESCC progression remains unexplored.
METHODS: The expression levels of MBNL1 and
QKI were examined in 28 tissue pairs from ESCC and adjacent normal tissues using data from the GEO database. Additionally, a total of 151 ESCC tissue samples, from stage T1 to T4, consisting of 13, 43, 87, and 8 cases per stage, respectively, were utilized for immunohistochemical (IHC) analysis. RNA sequencing was utilized to examine the expression profiles of circRNAs, lncRNAs, and mRNAs across 3 normal tissues, 3 ESCC tissues, and 3 pairs of KYSE150 cells in both wildtype (WT) and those with MBNL1 or QKI knockouts. Transwell, colony formation, and subcutaneous tumorigenesis assays assessed the impact of MBNL1 or
QKI knockout on ESCC cell migration, invasion, and proliferation.
RESULTS: ESCC onset significantly altered MBNL1 and QKI expression levels, influencing diverse RNA species. Elevated MBNL1 or
QKI expression correlated with patient age or tumor invasion depth, respectively. MBNL1 or QKI knockout markedly enhanced cancer cell migration, invasion, proliferation, and tumor growth. Moreover, the absence of either MBNL1 or QKI modulated the expression profiles of multiple circRNAs, causing extensive downstream alterations in the expression of numerous lncRNAs and mRNAs. While the functions of circRNA and lncRNA among the top 20 differentially expressed genes remain unclear, mRNAs like SLCO4C1, TMPRSS15, and MAGEB2 have reported associations with tumor progression.
CONCLUSIONS: This study underscores the tumor-suppressive roles of MBNL1 and QKI in ESCC, proposing them as potential biomarkers and therapeutic targets for ESCC diagnosis and treatment.