PDF(Pubmed)
Abstract：
BACKGROUND: N6-methyladenosine (m6A) modification represents the predominant alteration found in eukaryotic messenger RNA and plays a crucial role in the progression of various tumors. However, despite its significance, the comprehensive investigation of METTL5, a key m6A methyltransferase, in colorectal cancer (CRC) remains limited.
OBJECTIVE: To investigate the role of METTL5 in CRC.
METHODS: We assessed METTL5 expression levels in clinical samples obtained from CRC patients as well as in CRC cell lines. To elucidate the downstream targets of METTL5, we performed RNA-sequencing analysis coupled with correlation analysis, leading us to identify Toll-like receptor 8 (TLR8) as a potential downstream target. In vitro functional assessments of METTL5 and TLR8 were conducted using CCK-8 assays, scratch assays, as well as assays measuring cell migration and invasion.
RESULTS: Our findings reveal a pronounced upregulation of METTL5 expression in both CRC cells and tissues, which correlated significantly with an unfavorable prognosis. In vitro experiments unequivocally demonstrated the oncogenic role of METTL5, as evidenced by its promotion of CRC cell proliferation, invasion, and migration. Notably, we identified TLR8 as a downstream target of METTL5, and subsequent down-regulation of TLR8 led to a significant inhibition of CRC cell proliferation, invasion, and tumor growth.
CONCLUSIONS: The heightened expression of METTL5 in CRC is strongly associated with clinicopathological features and a poor prognosis, thereby underscoring its potential utility as a critical marker for facilitating early diagnosis and prognostication in CRC.
OBJECTIVE: To investigate the role of METTL5 in CRC.
METHODS: We assessed METTL5 expression levels in clinical samples obtained from CRC patients as well as in CRC cell lines. To elucidate the downstream targets of METTL5, we performed RNA-sequencing analysis coupled with correlation analysis, leading us to identify Toll-like receptor 8 (TLR8) as a potential downstream target. In vitro functional assessments of METTL5 and TLR8 were conducted using CCK-8 assays, scratch assays, as well as assays measuring cell migration and invasion.
RESULTS: Our findings reveal a pronounced upregulation of METTL5 expression in both CRC cells and tissues, which correlated significantly with an unfavorable prognosis. In vitro experiments unequivocally demonstrated the oncogenic role of METTL5, as evidenced by its promotion of CRC cell proliferation, invasion, and migration. Notably, we identified TLR8 as a downstream target of METTL5, and subsequent down-regulation of TLR8 led to a significant inhibition of CRC cell proliferation, invasion, and tumor growth.
CONCLUSIONS: The heightened expression of METTL5 in CRC is strongly associated with clinicopathological features and a poor prognosis, thereby underscoring its potential utility as a critical marker for facilitating early diagnosis and prognostication in CRC.
摘要：
背景：N6-甲基腺苷（m6A）修饰代表在真核信使RNA中发现的主要改变，并在各种肿瘤的进展中起关键作用。然而,尽管意义重大,METTL5是一种关键的m6A甲基转移酶，在结直肠癌（CRC）中仍然有限。
目的：探讨METTL5在CRC中的作用。
方法：我们评估了从CRC患者获得的临床样品以及CRC细胞系中的METTL5表达水平。为了阐明METTL5的下游靶标，我们进行了RNA测序分析和相关分析，引导我们将Toll样受体8（TLR8）鉴定为潜在的下游靶标。使用CCK-8测定进行METTL5和TLR8的体外功能评估，划痕试验,以及测定细胞迁移和侵袭。
结果：我们的发现揭示了在CRC细胞和组织中METTL5表达的显著上调，与不良预后显着相关。体外实验明确证明了METTL5的致癌作用，正如其促进CRC细胞增殖所证明的那样，入侵,和移民。值得注意的是,我们将TLR8确定为METTL5的下游靶标，随后下调TLR8导致CRC细胞增殖的显著抑制，入侵,和肿瘤生长。
结论：METTL5在CRC中的高表达与临床病理特征和不良预后密切相关，从而强调了其作为促进CRC早期诊断和预后的关键标志物的潜在效用。
目的：探讨METTL5在CRC中的作用。
方法：我们评估了从CRC患者获得的临床样品以及CRC细胞系中的METTL5表达水平。为了阐明METTL5的下游靶标，我们进行了RNA测序分析和相关分析，引导我们将Toll样受体8（TLR8）鉴定为潜在的下游靶标。使用CCK-8测定进行METTL5和TLR8的体外功能评估，划痕试验,以及测定细胞迁移和侵袭。
结果：我们的发现揭示了在CRC细胞和组织中METTL5表达的显著上调，与不良预后显着相关。体外实验明确证明了METTL5的致癌作用，正如其促进CRC细胞增殖所证明的那样，入侵,和移民。值得注意的是,我们将TLR8确定为METTL5的下游靶标，随后下调TLR8导致CRC细胞增殖的显著抑制，入侵,和肿瘤生长。
结论：METTL5在CRC中的高表达与临床病理特征和不良预后密切相关，从而强调了其作为促进CRC早期诊断和预后的关键标志物的潜在效用。
