miR-146a-5p inhibits proliferation and invasion of prostate cancer cell line PC-3 by targeting SMAD4
Objective To explore the inhibition effect and mechanism of miR-146a-5p on proliferation and invasion of prostate cancer (PCa) cell line PC-3 by targeting SMAD4. Methods RT-qPCR was used to detect the expression of miR-146a-5p in PCa tissues and cell lines. The relevance of miR-146a-5p expression...
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Format: | Article |
Language: | zho |
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Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.
2023-08-01
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Series: | Jichu yixue yu linchuang |
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Online Access: | http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2023-43-8-1215.pdf |
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author | LIU Bide, LI Xun, WANG Shuheng, JIN Hongyong, ZHANG Xiao'an, LI Jiuzhi |
author_facet | LIU Bide, LI Xun, WANG Shuheng, JIN Hongyong, ZHANG Xiao'an, LI Jiuzhi |
author_sort | LIU Bide, LI Xun, WANG Shuheng, JIN Hongyong, ZHANG Xiao'an, LI Jiuzhi |
collection | DOAJ |
description | Objective To explore the inhibition effect and mechanism of miR-146a-5p on proliferation and invasion of prostate cancer (PCa) cell line PC-3 by targeting SMAD4. Methods RT-qPCR was used to detect the expression of miR-146a-5p in PCa tissues and cell lines. The relevance of miR-146a-5p expression with Gleason score was also analyzed. MTT, BrdU experiment, cell colony formation experiment, scratch experiment, Transwell assay and nude mouse xenograft model experiment were conducted to detect the effect of miR-146a-5p on cell proliferation, tumorigenicity, migration and invasion. The expression of SMAD4 in PCa tissues was detected by RT-qPCR, and the targeting relationship of SMAD4 and miR-146a-5p was confirmed by double luciferase reporter gene assay and rescue experiment. Western blot was used to detect the expression of SMAD2/SMAD3 complex in nucleus affected by miR-146a-5p and SMAD4. Finally, double luciferase reporter gene assay and ChIP experiment were performed to examine the targeting regulation of TIM3 by miR-146a-5p/SMAD4/SMAD2/SMAD3 signaling axis. Results miR-146a-5p was low expressed in PCa tissues and cell lines; its expression was negatively correlated to Gleason score and had the lowest expression in PC-3 cells. miR-146a-5p inhibited the proliferation and invasion of PC-3 cells by targeting SMAD4. SMAD2/SMAD3/TIM3 axis seemed to be the downstream mechanism of miR-146a-5p/SMAD4 signaling pathway. Conclusions miR-146a-5p can inhibit the proliferation and invasion of PC-3 cells by targeting SMAD4, and the downstream mechanism might be related to the SMAD2/SMAD3/TIM3 signaling pathway. |
first_indexed | 2024-03-08T17:02:34Z |
format | Article |
id | doaj.art-00d8f2d0088b4f53a4cc8204fe379b7f |
institution | Directory Open Access Journal |
issn | 1001-6325 |
language | zho |
last_indexed | 2024-03-08T17:02:34Z |
publishDate | 2023-08-01 |
publisher | Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College. |
record_format | Article |
series | Jichu yixue yu linchuang |
spelling | doaj.art-00d8f2d0088b4f53a4cc8204fe379b7f2024-01-04T07:33:23ZzhoInstitute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.Jichu yixue yu linchuang1001-63252023-08-014381215122110.16352/j.issn.1001-6325.2023.08.1215miR-146a-5p inhibits proliferation and invasion of prostate cancer cell line PC-3 by targeting SMAD4LIU Bide, LI Xun, WANG Shuheng, JIN Hongyong, ZHANG Xiao'an, LI Jiuzhi0Department of Urology, Laboratory of Urology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, ChinaObjective To explore the inhibition effect and mechanism of miR-146a-5p on proliferation and invasion of prostate cancer (PCa) cell line PC-3 by targeting SMAD4. Methods RT-qPCR was used to detect the expression of miR-146a-5p in PCa tissues and cell lines. The relevance of miR-146a-5p expression with Gleason score was also analyzed. MTT, BrdU experiment, cell colony formation experiment, scratch experiment, Transwell assay and nude mouse xenograft model experiment were conducted to detect the effect of miR-146a-5p on cell proliferation, tumorigenicity, migration and invasion. The expression of SMAD4 in PCa tissues was detected by RT-qPCR, and the targeting relationship of SMAD4 and miR-146a-5p was confirmed by double luciferase reporter gene assay and rescue experiment. Western blot was used to detect the expression of SMAD2/SMAD3 complex in nucleus affected by miR-146a-5p and SMAD4. Finally, double luciferase reporter gene assay and ChIP experiment were performed to examine the targeting regulation of TIM3 by miR-146a-5p/SMAD4/SMAD2/SMAD3 signaling axis. Results miR-146a-5p was low expressed in PCa tissues and cell lines; its expression was negatively correlated to Gleason score and had the lowest expression in PC-3 cells. miR-146a-5p inhibited the proliferation and invasion of PC-3 cells by targeting SMAD4. SMAD2/SMAD3/TIM3 axis seemed to be the downstream mechanism of miR-146a-5p/SMAD4 signaling pathway. Conclusions miR-146a-5p can inhibit the proliferation and invasion of PC-3 cells by targeting SMAD4, and the downstream mechanism might be related to the SMAD2/SMAD3/TIM3 signaling pathway.http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2023-43-8-1215.pdfprostate cancer|mir-146a-5p|smad4|tim3 |
spellingShingle | LIU Bide, LI Xun, WANG Shuheng, JIN Hongyong, ZHANG Xiao'an, LI Jiuzhi miR-146a-5p inhibits proliferation and invasion of prostate cancer cell line PC-3 by targeting SMAD4 Jichu yixue yu linchuang prostate cancer|mir-146a-5p|smad4|tim3 |
title | miR-146a-5p inhibits proliferation and invasion of prostate cancer cell line PC-3 by targeting SMAD4 |
title_full | miR-146a-5p inhibits proliferation and invasion of prostate cancer cell line PC-3 by targeting SMAD4 |
title_fullStr | miR-146a-5p inhibits proliferation and invasion of prostate cancer cell line PC-3 by targeting SMAD4 |
title_full_unstemmed | miR-146a-5p inhibits proliferation and invasion of prostate cancer cell line PC-3 by targeting SMAD4 |
title_short | miR-146a-5p inhibits proliferation and invasion of prostate cancer cell line PC-3 by targeting SMAD4 |
title_sort | mir 146a 5p inhibits proliferation and invasion of prostate cancer cell line pc 3 by targeting smad4 |
topic | prostate cancer|mir-146a-5p|smad4|tim3 |
url | http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2023-43-8-1215.pdf |
work_keys_str_mv | AT liubidelixunwangshuhengjinhongyongzhangxiaoanlijiuzhi mir146a5pinhibitsproliferationandinvasionofprostatecancercelllinepc3bytargetingsmad4 |