Kai Lu1, Feiling Feng1, Yingcheng Yang2, Kai Liu1, Jicheng Duan1, Hu Liu1, Jiahe Yang1, Mengchao Wu3, Chen Liu4, Yanxin Chang5. 1. Biliary Tract Surgery Department, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, People's Republic of China. 2. Organ Transplantation Department, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, People's Republic of China. 3. Hepatic Surgery Department, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, People's Republic of China. 4. Biliary Tract Surgery Department, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, People's Republic of China. dinoliu@126.com. 5. Biliary Tract Surgery Department, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, People's Republic of China. pycmu402@163.com.
Abstract
BACKGROUND: Gallbladder carcinoma (GBC) is one of the most aggressive and lethal tumors, with extremely high metastatic activity and poor prognosis. Previously we have studied miRNAs that promote metastasis and progression of GBC, the aim of present study was to systematically elucidate the metastasis suppressor miRNAs in GBC. METHODS: A novel designed high-throughput screening method that combined high content screening (HCS) and miRNA microarray analysis was conducted to filter out anti-metastatic miRNAs of GBC. Frozen samples were analyzed for the expression of goal miRNAs by real-time PCR. The biological functions of miRNAs were studied by transwell, immunoblot. Liver metastasis model via spleen injection was further examined in nude mice. Kaplan-Meier and Cox regression analyses were used to analyze the effect of goal miRNAs on overall survival. The target genes and interaction network of goal miRNAs were determined by whole transcriptome genome sequencing. RESULTS: Out of the miRNAs library, a series of prominent metastatic suppressor miRNA candidates were filtered out. Among them, miR-7-2-3p and miR-29c-3p were discovered downregulated in GBC, and upregulation of them could reverse epithelial-mesenchymal transition and decrease the metastasis ability of GBC cells in vitro and in vivo, which was dominated by the miRNA-mRNA-lncRNA co-expression network. And DCLK1 and SLC36A1 are the direct target genes of miR-7-2-3p and miR-29c-3p. Moreover, the deficiency of miR-7-2-3p and miR-29c-3p was closely associated with poor prognosis of GBC patients. CONCLUSIONS: Our findings indicate that miR-7-2-3p and miR-29c-3p play crucial roles in the pathogenesis and worse prognosis of GBCs, which may serve as prognosis biomarkers and promise potential therapeutic targets in the future.
BACKGROUND:Gallbladder carcinoma (GBC) is one of the most aggressive and lethal tumors, with extremely high metastatic activity and poor prognosis. Previously we have studied miRNAs that promote metastasis and progression of GBC, the aim of present study was to systematically elucidate the metastasis suppressor miRNAs in GBC. METHODS: A novel designed high-throughput screening method that combined high content screening (HCS) and miRNA microarray analysis was conducted to filter out anti-metastatic miRNAs of GBC. Frozen samples were analyzed for the expression of goal miRNAs by real-time PCR. The biological functions of miRNAs were studied by transwell, immunoblot. Liver metastasis model via spleen injection was further examined in nude mice. Kaplan-Meier and Cox regression analyses were used to analyze the effect of goal miRNAs on overall survival. The target genes and interaction network of goal miRNAs were determined by whole transcriptome genome sequencing. RESULTS: Out of the miRNAs library, a series of prominent metastatic suppressor miRNA candidates were filtered out. Among them, miR-7-2-3p and miR-29c-3p were discovered downregulated in GBC, and upregulation of them could reverse epithelial-mesenchymal transition and decrease the metastasis ability of GBC cells in vitro and in vivo, which was dominated by the miRNA-mRNA-lncRNA co-expression network. And DCLK1 and SLC36A1 are the direct target genes of miR-7-2-3p and miR-29c-3p. Moreover, the deficiency of miR-7-2-3p and miR-29c-3p was closely associated with poor prognosis of GBCpatients. CONCLUSIONS: Our findings indicate that miR-7-2-3p and miR-29c-3p play crucial roles in the pathogenesis and worse prognosis of GBCs, which may serve as prognosis biomarkers and promise potential therapeutic targets in the future.
Authors: Soumya Luthra; Uma Chandran; Brenda Diergaarde; Michael Becich; Adrian V Lee; Carola A Neumann Journal: Free Radic Biol Med Date: 2018-03-12 Impact factor: 7.376
Authors: Tsz-Lun Yeung; Cecilia S Leung; Kay-Pong Yip; Chi Lam Au Yeung; Stephen T C Wong; Samuel C Mok Journal: Am J Physiol Cell Physiol Date: 2015-07-29 Impact factor: 4.249
Authors: Ma'mon M Hatmal; Mohammad A I Al-Hatamleh; Amin N Olaimat; Walhan Alshaer; Hanan Hasan; Khaled A Albakri; Enas Alkhafaji; Nada N Issa; Murad A Al-Holy; Salim M Abderrahman; Atiyeh M Abdallah; Rohimah Mohamud Journal: Biomedicines Date: 2022-05-24