Amplified LncRNA PVT1 promotes lung cancer proliferation and metastasis by facilitating VEGFC expression
| Autor: | Yanming Pan, Lantao Liu, Jianbo Yu, Yukuan Feng, Yongxia Cheng |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Lung Neoplasms
Cell Vascular Endothelial Growth Factor C Mice Nude Biology Biochemistry Metastasis 03 medical and health sciences Mice 0302 clinical medicine In vivo medicine Animals Humans RNA Neoplasm Neoplasm Metastasis Lung cancer Molecular Biology 030304 developmental biology Cell Proliferation 0303 health sciences Mice Inbred BALB C Cell growth Cell Biology medicine.disease PVT1 Neoplasm Proteins Blot Gene Expression Regulation Neoplastic medicine.anatomical_structure Vascular endothelial growth factor C A549 Cells 030220 oncology & carcinogenesis Cancer research RNA Long Noncoding |
| Zdroj: | Biochemistry and cell biology = Biochimie et biologie cellulaire. 98(6) |
| ISSN: | 1208-6002 |
| Popis: | Although the abundance of long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) in lung cancer has been well researched, the underlying mechanisms behind its effects were unknown. Here we investigated the molecular events regulating PVT1 in lung cancer. The pro-proliferative property of PVT1 was examined using a xenograft tumor model. Transwell chambers were used to analyze the impact of PVT1 expression on cell invasiveness and migration. In vivo metastasis was examined by tail-vein-injection in mice. Direct binding of miR-128 to PVT1 was investigated using a probe pulldown assay. The relative expression levels of miR-128 and PVT1 were quantified by real-time polymerase chain reaction and Western blotting. We show here that when PVT1 is amplified, there is a poor survival prognosis for patients with lung cancer. Elevated levels of PVT1 promoted lung cancer cell proliferation and metastasis, both in vitro and in vivo. Mechanistically, we found that PVT1 competes endogenously with miR-128 in the regulation of vascular endothelial growth factor C (VEGFC) expression, which is significantly associated with an unfavorable prognosis in lung cancer. We identified that copy number amplification significantly contributes to the high level of PVT1 transcripts in lung cancer, which promotes cell proliferation and metastatic behavior via modulating VEGFC expression by endogenous competition with miR-128. |
| Databáze: | OpenAIRE |
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