A novel LncRNA- LOC105371049 regulates colorectal cancer proliferation, metastasis and metabolism
Refereed conference paper presented and published in conference proceedings

香港中文大學研究人員

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摘要Background: Colorectal cancer (CRC) is one of the leading causes of cancer mortality with the increasing rate of incidence in China in recent years. The molecular alterations in CRC have been studied extensively. However, the molecular mechanisms of long non-coding RNA (LncRNA) involved in the tumorigenesis of CRC are still poorly understood. The aim of this study is to find the LncRNAs which are involved in CRC tumorigenesis. And the role and mechanism in CRC development and the potential value for targeted therapy will be investigated. In the present study, we investigated the role of LOC105371049 in CRC development.
Material and Methods: The expression of LOC105371049 were examined in both CRC cell lines (NCM460 as control) and tumor tissues (adjacent normal tissues as control) by real-time PCR. The whole sequence of LOC105371049 were determined by rapid-amplification of cDNA ends (RACE). Stably knock down (KD) or overexpression LOC105371049 cell lines were made by lentivirus. Cells proliferation, migration and metabolism were examined and compared by cell counting kit-8(CCK-8), foci formation, transwell assay and seahorse energy analysis experiments. The cells were transiently transfected with LOC105371049 siRNA. Real-time PCR and western blot experiments were conducted to examine the regulatory role of LOC105371049 on polycystin 1 (PKD1). Bioinformatics analysis were performed to check the expression and prognostic value of PKD1 in CRC tissues.
Results: LOC105371049 was found to be up-regulated in most of the CRC cell lines compared with normal epithelial cells NCM460. Its expression was upregulated in most of the CRC tissues (11/12). To evaluate the functional effect of LOC105371049 on CRC cells, stable LOC105371049 KD cell lines were made (three individual shRNA sequence). The proliferation study showed that KD LOC105371049 significantly inhibited the cells growth at 72 and 96 hours. And foci formation assay showed that KD LOC105371049 significantly inhibited cells colony formation. Transwell results showed that KD LOC105371049 could inhibit the migration of CRC cells HCT116. KD LOC105371049 expression also significantly inhibited the extra cellular acids rate (ECAR) of CRC cells. In addition, we found that silencing of LOC105371049 inhibited the expression of PKD1 at mRNA and protein level. We found that PKD1 expression was upregulated in Colon adenocarcinoma and correlated with poor survival rate in CRC patients by bioinformatic analysis (Oncomine and The human protein atalas).
Summary: Here, we have identified a novel LncRNA-LOC105371049 as an oncogenic type of non-coding RNA, which plays an important role during CRC development. Most importantly, PKD1 is identified as a potential novel target of LOC105371049. They may serve as a novel therapeutic target for CRC patients.
著者Hongyan YU, Xiangqi MENG, Xiaoqiang YAO
會議名稱ESMO 21st World Congress on Gastrointestinal Cancer
會議開始日03.07.2019
會議完結日06.07.2019
會議地點Barcelona
會議國家/地區西班牙
會議論文集題名ANNALS OF ONCOLOGY
出版年份2019
月份7
卷號30
期次Suppl 4
國際標準期刊號0923-7534
電子國際標準期刊號1569-8041
語言美式英語

上次更新時間 2019-22-10 於 12:02