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LncRNA XIST acts as a ceRNA sponging miR-185-5p to modulate pancreatic cancer cell proliferation via targeting CCND2

BACKGROUND: Long non-coding RNAs (lncRNAs) have been proved to be involved in the occurrence and progression of various tumors including pancreatic cancer (PC). Growing evidence shows that lncRNA X inactive-specific transcript (XIST) functions as an oncogene in multiple tumorigenesis. However, the u...

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Autores principales: Wang, Ya-Peng, Huang, Yan, Hou, Tao, Lu, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8798058/
https://www.ncbi.nlm.nih.gov/pubmed/35117490
http://dx.doi.org/10.21037/tcr.2020.01.26
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author Wang, Ya-Peng
Huang, Yan
Hou, Tao
Lu, Min
author_facet Wang, Ya-Peng
Huang, Yan
Hou, Tao
Lu, Min
author_sort Wang, Ya-Peng
collection PubMed
description BACKGROUND: Long non-coding RNAs (lncRNAs) have been proved to be involved in the occurrence and progression of various tumors including pancreatic cancer (PC). Growing evidence shows that lncRNA X inactive-specific transcript (XIST) functions as an oncogene in multiple tumorigenesis. However, the underlying mechanism of lncRNA XIST in the progression of PC remains elusive. METHODS: Expression levels of XIST and miR-185-5p both in PC tissues or PC cells were determined using real-time quantitative PCR (qRT-PCR). Gain and loss-of-function of XIST or miR-185-5p was performed for further exploration. Moreover, colony formation assay was performed to assess cell proliferation. Flow cytometry analysis was performed to measure cell cycle and apoptosis. Dual-luciferase reporter assay was conducted to verify the correlation between XIST, miR-185-5p and CCND2, respectively. Additionally, western blot analysis was conducted to determine the expression pattern of apoptosis-related proteins and cell cycle-associated proteins. RESULTS: Herein, we found that XIST expression was up-regulated while miR-185-5p was down-regulated both in PC tissues and cell lines, compared with that of controls. Moreover, there was a negative correlation between XIST and miR-185-5p. Following that, functional experiments displayed that knockdown of XIST or overexpression of miR-185-5p inhibited cell proliferation, induced cell cycle arrest and promoted apoptosis in PC cells. Furthermore, mechanistic experiments displayed that XIST could negatively regulate miR-185-5p via direct binding. In addition, CCND2 was shown to be a downstream target of miR-185-5p. Importantly, overexpression or knockdown of XIST significantly increased or decreased the expression of CCND2, while these effects were reversed by miR-185-5p. CONCLUSIONS: Taken together, our study demonstrated that lncRNA XIST functions as an oncogene and exerts its regulation via miR-185-5p/CCND2 axis, promoting proliferation and inhibiting apoptosis in PC.
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spelling pubmed-87980582022-02-02 LncRNA XIST acts as a ceRNA sponging miR-185-5p to modulate pancreatic cancer cell proliferation via targeting CCND2 Wang, Ya-Peng Huang, Yan Hou, Tao Lu, Min Transl Cancer Res Original Article BACKGROUND: Long non-coding RNAs (lncRNAs) have been proved to be involved in the occurrence and progression of various tumors including pancreatic cancer (PC). Growing evidence shows that lncRNA X inactive-specific transcript (XIST) functions as an oncogene in multiple tumorigenesis. However, the underlying mechanism of lncRNA XIST in the progression of PC remains elusive. METHODS: Expression levels of XIST and miR-185-5p both in PC tissues or PC cells were determined using real-time quantitative PCR (qRT-PCR). Gain and loss-of-function of XIST or miR-185-5p was performed for further exploration. Moreover, colony formation assay was performed to assess cell proliferation. Flow cytometry analysis was performed to measure cell cycle and apoptosis. Dual-luciferase reporter assay was conducted to verify the correlation between XIST, miR-185-5p and CCND2, respectively. Additionally, western blot analysis was conducted to determine the expression pattern of apoptosis-related proteins and cell cycle-associated proteins. RESULTS: Herein, we found that XIST expression was up-regulated while miR-185-5p was down-regulated both in PC tissues and cell lines, compared with that of controls. Moreover, there was a negative correlation between XIST and miR-185-5p. Following that, functional experiments displayed that knockdown of XIST or overexpression of miR-185-5p inhibited cell proliferation, induced cell cycle arrest and promoted apoptosis in PC cells. Furthermore, mechanistic experiments displayed that XIST could negatively regulate miR-185-5p via direct binding. In addition, CCND2 was shown to be a downstream target of miR-185-5p. Importantly, overexpression or knockdown of XIST significantly increased or decreased the expression of CCND2, while these effects were reversed by miR-185-5p. CONCLUSIONS: Taken together, our study demonstrated that lncRNA XIST functions as an oncogene and exerts its regulation via miR-185-5p/CCND2 axis, promoting proliferation and inhibiting apoptosis in PC. AME Publishing Company 2020-03 /pmc/articles/PMC8798058/ /pubmed/35117490 http://dx.doi.org/10.21037/tcr.2020.01.26 Text en 2020 Translational Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
spellingShingle Original Article
Wang, Ya-Peng
Huang, Yan
Hou, Tao
Lu, Min
LncRNA XIST acts as a ceRNA sponging miR-185-5p to modulate pancreatic cancer cell proliferation via targeting CCND2
title LncRNA XIST acts as a ceRNA sponging miR-185-5p to modulate pancreatic cancer cell proliferation via targeting CCND2
title_full LncRNA XIST acts as a ceRNA sponging miR-185-5p to modulate pancreatic cancer cell proliferation via targeting CCND2
title_fullStr LncRNA XIST acts as a ceRNA sponging miR-185-5p to modulate pancreatic cancer cell proliferation via targeting CCND2
title_full_unstemmed LncRNA XIST acts as a ceRNA sponging miR-185-5p to modulate pancreatic cancer cell proliferation via targeting CCND2
title_short LncRNA XIST acts as a ceRNA sponging miR-185-5p to modulate pancreatic cancer cell proliferation via targeting CCND2
title_sort lncrna xist acts as a cerna sponging mir-185-5p to modulate pancreatic cancer cell proliferation via targeting ccnd2
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8798058/
https://www.ncbi.nlm.nih.gov/pubmed/35117490
http://dx.doi.org/10.21037/tcr.2020.01.26
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