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- Title
Long noncoding RNA SOX2OT promotes the proliferation of pancreatic cancer by binding to FUS.
- Authors
Chen, Lei; Zhang, Jingjing; Chen, Qun; Ge, Wanli; Meng, Lingdong; Huang, Xumin; Shen, Peng; Yuan, Hao; Shi, Guodong; Miao, Yi; Jiang, Kuirong
- Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors has one of the worst prognoses, and the role of long noncoding RNAs (lncRNAs) in the biological and pathological processes of pancreatic cancer, including tumor cell proliferation, is a popular topic in tumor research. Our previous study revealed the correlation between high levels of the lncRNA‐SOX2OT (SOX2OT) with poor survival outcomes. Cell Counting Kit‐8, EdU, Flow cytometry and Colony formation assays as well as Xenograft growth of PDAC cells in mice were used for the detection of PDAC cells proliferation progression. Fluorescence in situ hybridization, RNA‐binding protein pulldown and RNA immunoprecipitation assays were also used to identify the putative mechanisms of SOX2OT participating in the tumor progression. SOX2OT and its potential downstream targets were verified by Western blot and quantitative real‐time polymerase chain reaction (qRT‐PCR). SOX2OT was confirmed to promote the proliferation of PDAC cells. It was found to directly physically bind to FUS and we also demonstrated that FUS protein stability was affected by binding with SOX2OT and FUS could suppressed PDAC tumor by regulating cell cycle‐associated factors CCND1 and p27. Our findings suggest that SOX2OT may act as a tumor promoter in PDAC through physically binding FUS and regulating its downstream cell cycle‐associated factors CCND1 and p27. It may serve as an effective target for antitumor treatment for pancreatic cancer. What's new? A large number of long noncoding RNAs (lncRNAs) have been shown to regulate tumor proliferation and progression in various cancers. However, the role of lncRNAs in pancreatic cancer remains to be fully elucidated. Here, the authors demonstrate that lncRNA SOX2OT can promote the proliferation of pancreatic cancer cells via direct interaction with the RNA‐binding protein FUS. SOX2OT bonding affects the protein stability of FUS, with FUS subsequently supporting proliferation by regulating cell cycle‐associated factors CCND1 and p27. The results reveal the involvement of the SOX2OT‐FUS‐CCND1/p27 axis in pancreatic tumorigenesis, which may help develop new approaches for human pancreatic cancer therapy.
- Subjects
PANCREATIC cancer; NON-coding RNA; SYNCRIP protein; CANCER cell proliferation; FLUORESCENCE in situ hybridization; PROTEIN stability
- Publication
International Journal of Cancer, 2020, Vol 147, Issue 1, p175
- ISSN
0020-7136
- Publication type
Article
- DOI
10.1002/ijc.32827