Department of Gastrointestinal Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan Province, China.
Department of Interventional Therapy, the First Affiliated Hospital of Xinxiang Medical College, Xinxiang, Henan Province, China.
PLoS One. 2023 Jun 22;18(6):e0287133. doi: 10.1371/journal.pone.0287133. eCollection 2023.
Long non-coding RNAs (lncRNAs) have been revealed to harbor open reading frames (ORFs) that can be translated into small peptides. The peptides may participate in the pathogenesis of colorectal cancer (CRC). Herein, we investigated the role of a lncRNA BVES-AS1-encoded peptide in colorectal tumorigenesis. Through bioinformatic analysis, lncRNA BVES-AS1 was predicted to have encoding potential and to be associated with poor prognosis of patients with CRC. In CRC cells, BVES-AS1 was validated to encode a 50-aa-length micro-peptide, named BVES-AS1-201-50aa, through a western blotting method. BVES-AS1-201-50aa enhanced cell viability and promoted the migratory and invasive capacities of HCT116 and SW480 CRC cells in vitro, validated via CCK-8 assay and transwell assay, respectively. Immunofluorescence assay showed that BVES-AS1-201-50aa increased the expression of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase 9 (MMP9) in CRC cells. We further verified that BVES-AS1-201-50aa targeted and activated the Src/mTOR signaling pathway in CRC cells by co-immunoprecipitation (Co-IP) experiment, qualitative proteomic analysis, and western blotting. Our findings demonstrated that BVES-AS1 could encode a micro-peptide, which promoted CRC cell viability, migration, and invasion in vitro. Our current work broadens the diversity and breadth of lncRNAs in human carcinogenesis.
长链非编码 RNA(lncRNA)被揭示含有开放阅读框(ORF),这些 ORF 可以被翻译成小肽。这些肽可能参与结直肠癌(CRC)的发病机制。在此,我们研究了 lncRNA BVES-AS1 编码的肽在结直肠肿瘤发生中的作用。通过生物信息学分析,预测 lncRNA BVES-AS1 具有编码潜力,并与 CRC 患者的预后不良相关。在 CRC 细胞中,通过 Western blot 方法验证 lncRNA BVES-AS1 编码一个 50 个氨基酸长度的微肽,命名为 BVES-AS1-201-50aa。BVES-AS1-201-50aa 通过 CCK-8 测定和 Transwell 测定分别增强了 HCT116 和 SW480 CRC 细胞的体外细胞活力,并促进了它们的迁移和侵袭能力。免疫荧光测定显示,BVES-AS1-201-50aa 增加了 CRC 细胞中增殖细胞核抗原(PCNA)和基质金属蛋白酶 9(MMP9)的表达。我们通过共免疫沉淀(Co-IP)实验、定性蛋白质组学分析和 Western blot 进一步验证了 BVES-AS1-201-50aa 靶向并激活了 CRC 细胞中的 Src/mTOR 信号通路。我们的研究结果表明,BVES-AS1 可以编码一种微肽,这种微肽可以促进 CRC 细胞在体外的活力、迁移和侵袭。我们目前的工作拓宽了 lncRNA 在人类癌症发生中的多样性和广度。