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miR-32-5p suppresses the proliferation and migration of pancreatic adenocarcinoma cells by targeting TLDC1

Pancreatic adenocarcinoma (PAAD) is one of the most fatal types of cancer in humans. However, the molecular mechanisms underlying the migration and invasion abilities of PAAD cells remain unclear. The aim of the present study was to explore the regulatory roles of microRNA (miR)-32-5p in PAAD cells....

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Autores principales: Yuan, Peng, Tang, Chaofeng, Chen, Bendong, Lei, Peng, Song, Jianjun, Xin, Guojun, Wang, Zuozheng, Hui, Yongfeng, Yao, Weijie, Wang, Genwang, Zhao, Guozhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430301/
https://www.ncbi.nlm.nih.gov/pubmed/34468015
http://dx.doi.org/10.3892/mmr.2021.12392
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author Yuan, Peng
Tang, Chaofeng
Chen, Bendong
Lei, Peng
Song, Jianjun
Xin, Guojun
Wang, Zuozheng
Hui, Yongfeng
Yao, Weijie
Wang, Genwang
Zhao, Guozhong
author_facet Yuan, Peng
Tang, Chaofeng
Chen, Bendong
Lei, Peng
Song, Jianjun
Xin, Guojun
Wang, Zuozheng
Hui, Yongfeng
Yao, Weijie
Wang, Genwang
Zhao, Guozhong
author_sort Yuan, Peng
collection PubMed
description Pancreatic adenocarcinoma (PAAD) is one of the most fatal types of cancer in humans. However, the molecular mechanisms underlying the migration and invasion abilities of PAAD cells remain unclear. The aim of the present study was to explore the regulatory roles of microRNA (miR)-32-5p in PAAD cells. miR-32-5p mimic and inhibitor were used to transfect the human PAAD AsPC-1 cell line to determine the role of miR-32-5p in cell proliferation and metastasis. The starBase database predicted the binding of miR-32-5p to the target gene TBC/LysM-associated domain containing 1 (TLDC1). Further analyses were performed to assess miR-32-5p and TLDC1 expression levels in healthy and PAAD tissues, as well as the association between miR-32-5p or TLDC1 expression and the prognosis of patients with PAAD. The interaction between miR-32-5p and TLDC1 was verified using the dual-luciferase reporter assay. miR-32-5p and TLDC1 expression levels were detected by reverse transcription-quantitative PCR and western blotting, respectively. The Cell Counting Kit-8 assay was utilised to assess cell proliferation, whereas the wound-healing and Transwell assays were conducted to assess cell migration and invasion, respectively. miR-32-5p expression levels were markedly lower in PAAD tissue compared with those in healthy tissue, and were significantly lower in PAAD cell lines compared with those in the human pancreatic duct cell line HPDE6, which corresponded with poor prognosis. miR-32-5p significantly inhibited the proliferation of PAAD cells and markedly reduced migration and invasion compared with the negative controls. miR-32-5p was shown to target TLDC1, with miR-32-5p expression in PAAD being negatively correlated with TLDC1 expression. High TLDC1 expression levels were associated with a poorer prognosis compared with low TLDC1 expression levels. Co-transfection of miR-32-5p mimic and pcDNA/TLDC1 demonstrated that TLDC1 significantly reversed miR-32-5p-mediated inhibition of the proliferation, migration and invasion of PAAD cells. Overall, the present study demonstrated that miR-32-5p may serve as a tumor-suppressor gene by inhibiting the proliferation and migration and invasion of PAAD cells via the downregulation of TLDC1. Therefore, miR-32-5p may serve as a potential diagnostic or prognostic marker for PAAD.
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spelling pubmed-84303012021-09-23 miR-32-5p suppresses the proliferation and migration of pancreatic adenocarcinoma cells by targeting TLDC1 Yuan, Peng Tang, Chaofeng Chen, Bendong Lei, Peng Song, Jianjun Xin, Guojun Wang, Zuozheng Hui, Yongfeng Yao, Weijie Wang, Genwang Zhao, Guozhong Mol Med Rep Articles Pancreatic adenocarcinoma (PAAD) is one of the most fatal types of cancer in humans. However, the molecular mechanisms underlying the migration and invasion abilities of PAAD cells remain unclear. The aim of the present study was to explore the regulatory roles of microRNA (miR)-32-5p in PAAD cells. miR-32-5p mimic and inhibitor were used to transfect the human PAAD AsPC-1 cell line to determine the role of miR-32-5p in cell proliferation and metastasis. The starBase database predicted the binding of miR-32-5p to the target gene TBC/LysM-associated domain containing 1 (TLDC1). Further analyses were performed to assess miR-32-5p and TLDC1 expression levels in healthy and PAAD tissues, as well as the association between miR-32-5p or TLDC1 expression and the prognosis of patients with PAAD. The interaction between miR-32-5p and TLDC1 was verified using the dual-luciferase reporter assay. miR-32-5p and TLDC1 expression levels were detected by reverse transcription-quantitative PCR and western blotting, respectively. The Cell Counting Kit-8 assay was utilised to assess cell proliferation, whereas the wound-healing and Transwell assays were conducted to assess cell migration and invasion, respectively. miR-32-5p expression levels were markedly lower in PAAD tissue compared with those in healthy tissue, and were significantly lower in PAAD cell lines compared with those in the human pancreatic duct cell line HPDE6, which corresponded with poor prognosis. miR-32-5p significantly inhibited the proliferation of PAAD cells and markedly reduced migration and invasion compared with the negative controls. miR-32-5p was shown to target TLDC1, with miR-32-5p expression in PAAD being negatively correlated with TLDC1 expression. High TLDC1 expression levels were associated with a poorer prognosis compared with low TLDC1 expression levels. Co-transfection of miR-32-5p mimic and pcDNA/TLDC1 demonstrated that TLDC1 significantly reversed miR-32-5p-mediated inhibition of the proliferation, migration and invasion of PAAD cells. Overall, the present study demonstrated that miR-32-5p may serve as a tumor-suppressor gene by inhibiting the proliferation and migration and invasion of PAAD cells via the downregulation of TLDC1. Therefore, miR-32-5p may serve as a potential diagnostic or prognostic marker for PAAD. D.A. Spandidos 2021-11 2021-08-31 /pmc/articles/PMC8430301/ /pubmed/34468015 http://dx.doi.org/10.3892/mmr.2021.12392 Text en Copyright: © Yuan et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Yuan, Peng
Tang, Chaofeng
Chen, Bendong
Lei, Peng
Song, Jianjun
Xin, Guojun
Wang, Zuozheng
Hui, Yongfeng
Yao, Weijie
Wang, Genwang
Zhao, Guozhong
miR-32-5p suppresses the proliferation and migration of pancreatic adenocarcinoma cells by targeting TLDC1
title miR-32-5p suppresses the proliferation and migration of pancreatic adenocarcinoma cells by targeting TLDC1
title_full miR-32-5p suppresses the proliferation and migration of pancreatic adenocarcinoma cells by targeting TLDC1
title_fullStr miR-32-5p suppresses the proliferation and migration of pancreatic adenocarcinoma cells by targeting TLDC1
title_full_unstemmed miR-32-5p suppresses the proliferation and migration of pancreatic adenocarcinoma cells by targeting TLDC1
title_short miR-32-5p suppresses the proliferation and migration of pancreatic adenocarcinoma cells by targeting TLDC1
title_sort mir-32-5p suppresses the proliferation and migration of pancreatic adenocarcinoma cells by targeting tldc1
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430301/
https://www.ncbi.nlm.nih.gov/pubmed/34468015
http://dx.doi.org/10.3892/mmr.2021.12392
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