Wei Zhan1, Xin Liao2, Zhongsheng Chen3, Lianghe Li3, Tian Tian3, Lei Yu4, Rui Li5. 1. Surgery of Colorectal, Affiliated Hospital of Guizhou Medical University, Guiyang City, 550004, Guizhou, China. 2. Department of Imaging, Affiliated Hospital of Guizhou Medical University, Guiyang City, 550004, Guizhou, China. 3. Graduate Student of Surgery, Guizhou Medical University, Guiyang City, 550004, Guizhou, China. 4. Department of Pathology, Guiyang Maternal and Child Health Hospital, Guiyang City, 550004, Guizhou, China. 5. Department of Traditional Chinese Medicine, Guizhou Provincial People's Hospital, Zhongshan East Road 83, Guiyang, 550002, People's Republic of China. RuiLidfg@163.com.
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.
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 CRCpatients. 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.