Upregulation of LINC02154 promotes esophageal cancer progression by enhancing cell cycling and epithelial-mesenchymal transition

IF 5.9 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Kotoha Shimote , Takeshi Niinuma , Hiroshi Kitajima , Kazuya Ishiguro , Eiichiro Yamamoto , Gota Sudo , Akira Yorozu , Mutsumi Toyota , Masahiro Kai , Masashi Idogawa , Hiromu Suzuki
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引用次数: 0

Abstract

Long noncoding RNAs (lncRNAs) play crucial roles in the progression of human malignancies; however, their involvement in esophageal cancer (ESCA) remains incompletely understood. In this study, we screened for lncRNAs upregulated in ESCA and identified 12 lncRNAs significantly upregulated in primary ESCA tumors. Among those, elevated LINC02154 expression correlated positively with advanced T stages. LINC02154 knockdown in ESCA cell lines suppressed cell proliferation and migration, while ectopic expression of LINC02154 enhanced colony formation. Depletion of LINC02154 suppressed genes involved in various oncogenic processes, including cell cycling, epithelial-mesenchymal transition (EMT), and metabolism. We also found that LINC02154 promotes EMT and enhances chemoresistance, at least in part, through suppression of miR-200b. Finally, RNA-pulldown and mass spectrometry analysis revealed that LINC02154 interacts with proteins involved in the cornified envelope or desmosome. These findings suggest that LINC02154 exerts oncogenic effects through modulation of multiple oncogenic signaling pathways in ESCA and that LINC02154 is a potential therapeutic target.
上调LINC02154通过增强细胞周期和上皮-间质转化促进食管癌进展
长链非编码rna (lncRNAs)在人类恶性肿瘤的进展中起着至关重要的作用;然而,它们在食管癌(ESCA)中的作用仍不完全清楚。在本研究中,我们筛选了ESCA中上调的lncrna,并鉴定出12个在原发性ESCA肿瘤中显著上调的lncrna。其中,LINC02154表达升高与晚期T分期呈正相关。在ESCA细胞系中,敲低LINC02154抑制细胞增殖和迁移,而异位表达LINC02154促进集落形成。LINC02154抑制基因的缺失涉及各种致癌过程,包括细胞周期、上皮-间质转化(EMT)和代谢。我们还发现LINC02154促进EMT并增强化疗耐药,至少部分是通过抑制miR-200b。最后,rna -pull和质谱分析显示,LINC02154与角化包膜或桥粒中涉及的蛋白质相互作用。这些发现表明,LINC02154通过调节ESCA中的多种致癌信号通路发挥致癌作用,并且LINC02154是一个潜在的治疗靶点。
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来源期刊
Non-coding RNA Research
Non-coding RNA Research Medicine-Biochemistry (medical)
CiteScore
7.70
自引率
6.00%
发文量
39
审稿时长
49 days
期刊介绍: Non-coding RNA Research aims to publish high quality research and review articles on the mechanistic role of non-coding RNAs in all human diseases. This interdisciplinary journal will welcome research dealing with all aspects of non-coding RNAs-their biogenesis, regulation and role in disease progression. The focus of this journal will be to publish translational studies as well as well-designed basic studies with translational and clinical implications. The non-coding RNAs of particular interest will be microRNAs (miRNAs), small interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs), U-RNAs/small nuclear RNAs (snRNAs), exosomal/extracellular RNAs (exRNAs), Piwi-interacting RNAs (piRNAs) and long non-coding RNAs. Topics of interest will include, but not limited to: -Regulation of non-coding RNAs -Targets and regulatory functions of non-coding RNAs -Epigenetics and non-coding RNAs -Biological functions of non-coding RNAs -Non-coding RNAs as biomarkers -Non-coding RNA-based therapeutics -Prognostic value of non-coding RNAs -Pharmacological studies involving non-coding RNAs -Population based and epidemiological studies -Gene expression / proteomics / computational / pathway analysis-based studies on non-coding RNAs with functional validation -Novel strategies to manipulate non-coding RNAs expression and function -Clinical studies on evaluation of non-coding RNAs The journal will strive to disseminate cutting edge research, showcasing the ever-evolving importance of non-coding RNAs in modern day research and medicine.
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