Abstract
Objectives
LncRNAs (long noncoding RNAs) have been reported to critically regulate colorectal cancer (CRC). We prospectively investigated effects and mechanisms of lncRNA LINC00858 on regulation of CRC progression.
Methods
Expression of LINC00858 and its target were analyzed by quantitative real-time polymerase chain reaction and in situ hybridization. MTT and bromodeoxyuridine/5-bromo-2′-deoxyuridine (BrdU) staining to assess cell proliferation ability. Flow cytometry, wound healing, and transwell assays were conducted to evaluate cell apoptosis, migration, and invasion, respectively. Interaction between LINC00858 and its target was confirmed by luciferase activity assay and RNA immunoprecipitation. Subcutaneous xenotransplanted tumor model was established and employed to detect tumorigenic functions of LINC00858, and further evaluated by qRT-PCR, western blot, immunohistochemistry, and hematoxylin and eosin staining.
Results
With a predicted poor prognosis, LINC00858 was upregulated in CRC patients. LINC00858 knockdown suppressed cell proliferation, invasion, and migration abilities, meanwhile induced cell apoptosis. Moreover, LINC00858 could target and inhibit the miR-4766-5p expression, thus promoting CRC progression. miR-4766-5p further suppressed serine/threonine kinase PAK2. Interestingly, interference of LINC00858 suppressed tumorigenic ability of CRC in vivo by downregulating PAK2.
Conclusions
LINC00858 promoted CRC progression by sponging miR-4766 to upregulate PAK2, shedding lights on LINC00858 as a potential therapeutic target candidate in CRC treatment from bench to clinic.
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Funding
This work was supported by Special Project of Academic New Seedling Cultivation and Innovation Exploration of Guizhou Medical University (Grant No. [2018]5779-30), Science and Technology Fund Project of Guizhou Health and Family Planning Commission (Grant No. gzwjkj-2018-1-035), Science and Technology Fund Project of Guizhou Health and Family Planning Commission (Grant No. gzwjkj-2018-1-075), State science and technology plan project of Qiandongnan Prefecture in 2019(145) and State science and technology plan project of Qiandongnan Prefecture in 2019(146).
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Wei Zhan and Xin Liao and Rui Li conceived and designed the experiments, Tian Tian analyzed and interpreted the results of the experiments, Cheng Zhongsheng and LiangheLi and Lei Yu performed the experiments.
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The present study was approved by the Ethics Committee on Drug Clinical Trials in Affiliated Hospital of Guizhou Medical University (Approval No. 2018-123-01). Written informed consent was obtained from each of the participants. All methods were performed in accordance with the relevant guidelines and regulations as per the instructions of the Ethical Research Board.
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Zhan, W., Liao, X., Chen, Z. et al. LINC00858 promotes colorectal cancer by sponging miR-4766-5p to regulate PAK2. Cell Biol Toxicol 36, 333–347 (2020). https://doi.org/10.1007/s10565-019-09506-3
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DOI: https://doi.org/10.1007/s10565-019-09506-3