Santosh Lamichhane1, Ji-Su Mo2, Grinsun Sharma1, Tae-Young Choi1, Soo-Cheon Chae3,4. 1. Department of Pathology, School of Medicine, Wonkwang University, Iksan, Chonbuk, 54538, Republic of Korea. 2. Digestive Disease Research Institute, Wonkwang University, Iksan, Chonbuk, 54538, Republic of Korea. 3. Department of Pathology, School of Medicine, Wonkwang University, Iksan, Chonbuk, 54538, Republic of Korea. chaesc@wku.ac.kr. 4. Digestive Disease Research Institute, Wonkwang University, Iksan, Chonbuk, 54538, Republic of Korea. chaesc@wku.ac.kr.
Abstract
OBJECTIVE: MicroRNAs are a class of small, non-coding RNAs that play a key role in several biological and molecular processes, including tumorigenesis. We previously identified that MIR452 is upregulated in both colorectal cancer (CRC) and colitis. However, the functional mechanisms of MIR452 and its target genes in CRC and colitis are not well understood. So, we hypothesize that MIR452 can influence CRC and DSS-induced colitis model through the regulation of IL20RA and its downstream JAK-STATs signaling pathway. METHODS: We used a luciferase reporter assay to confirm the effect of MIR452 on IL20RA expression. The protein and mRNA expression of a target gene and its associated molecules were measured by western blot, quantitative RT-PCR, and immunohistochemistry. RESULTS: We found that the IL20RA was a direct target gene of MIR452. Overexpression of MIR452 in CRC cell lines significantly decreased IL20RA and its downstream Janus kinase 1 (JAK1), Signal transducer and activator of transcription 1 (STAT1) and STAT3. Knockdown of IL20RA in CRC cell lines by IL20RA gene silencing also decreased the expression of IL20RA, JAK1, and STAT3, but not of STAT1. CONCLUSION: Our results suggest that MIR452 regulates STAT3 through the IL20RA-mediated JAK1 pathway, but not STAT1. Overall, MIR452 acts as tumor suppressor in human CRC and in a mouse colitis model. These findings suggest that MIR452 is a promising therapeutic target in the treatment of cancer and colitis.
OBJECTIVE: MicroRNAs are a class of small, non-coding RNAs that play a key role in several biological and molecular processes, including tumorigenesis. We previously identified that MIR452 is upregulated in both colorectal cancer (CRC) and colitis. However, the functional mechanisms of MIR452 and its target genes in CRC and colitis are not well understood. So, we hypothesize that MIR452 can influence CRC and DSS-induced colitis model through the regulation of IL20RA and its downstream JAK-STATs signaling pathway. METHODS: We used a luciferase reporter assay to confirm the effect of MIR452 on IL20RA expression. The protein and mRNA expression of a target gene and its associated molecules were measured by western blot, quantitative RT-PCR, and immunohistochemistry. RESULTS: We found that the IL20RA was a direct target gene of MIR452. Overexpression of MIR452 in CRC cell lines significantly decreased IL20RA and its downstream Janus kinase 1 (JAK1), Signal transducer and activator of transcription 1 (STAT1) and STAT3. Knockdown of IL20RA in CRC cell lines by IL20RA gene silencing also decreased the expression of IL20RA, JAK1, and STAT3, but not of STAT1. CONCLUSION: Our results suggest that MIR452 regulates STAT3 through the IL20RA-mediated JAK1 pathway, but not STAT1. Overall, MIR452 acts as tumor suppressor in human CRC and in a mouse colitis model. These findings suggest that MIR452 is a promising therapeutic target in the treatment of cancer and colitis.
Authors: Jun Lu; Gad Getz; Eric A Miska; Ezequiel Alvarez-Saavedra; Justin Lamb; David Peck; Alejandro Sweet-Cordero; Benjamin L Ebert; Raymond H Mak; Adolfo A Ferrando; James R Downing; Tyler Jacks; H Robert Horvitz; Todd R Golub Journal: Nature Date: 2005-06-09 Impact factor: 49.962
Authors: Eleonora A Braga; Marina V Fridman; Vitaly I Loginov; Alexey A Dmitriev; Sergey G Morozov Journal: Front Genet Date: 2019-04-24 Impact factor: 4.599