circ-SIRT1 Promotes Colorectal Cancer Proliferation and EMT by Recruiting and Binding to eIF4A3

Circular RNA (circRNA), a recently identified type of endogenous noncoding RNA, has been implicated in the occurrence and development of a variety of tumors; however, whether circ-SIRT1, derived from pre-mRNA of the parental SIRT1 gene, is involved in colorectal cancer (CRC) remains unknown, as do t...

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Main Authors: Xiangjie Wang, Shuang Liu, Bin Xu, Yabin Liu, Peng Kong, Changlin Li, Binghui Li
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Analytical Cellular Pathology
Online Access:http://dx.doi.org/10.1155/2021/5739769
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author Xiangjie Wang
Shuang Liu
Bin Xu
Yabin Liu
Peng Kong
Changlin Li
Binghui Li
author_facet Xiangjie Wang
Shuang Liu
Bin Xu
Yabin Liu
Peng Kong
Changlin Li
Binghui Li
author_sort Xiangjie Wang
collection DOAJ
description Circular RNA (circRNA), a recently identified type of endogenous noncoding RNA, has been implicated in the occurrence and development of a variety of tumors; however, whether circ-SIRT1, derived from pre-mRNA of the parental SIRT1 gene, is involved in colorectal cancer (CRC) remains unknown, as do the potential underlying mechanisms. The expression of circ-SIRT1 in CRC cells and tissue was detected by RT-qPCR. Colony formation and Cell Counting Kit-8 assays were used to evaluate the effect of circ-SIRT1 knockdown on the proliferative ability of CRC cells. Wound healing and Transwell assays were used to assess the effect of circ-SIRT1 knockdown on the migratory and invasive capacity of CRC cells. RNA immunoprecipitation and RNA pull-down assays were employed to validate the binding of circ-SIRT1 to EIF4A3. Western blot was used to identify the changes in the expression of EIF4A3 and EMT-related proteins. The RT-qPCR results showed that circ-SIRT1 was highly expressed in CRC cells and tissue and was positively correlated with the depth of tumor invasion. Knocking down circ-SIRT1 inhibited the proliferation and invasion of CRC cells and EMT. We further found that EIF4A3 could bind to circ-SIRT1, and that overexpressing circ-SIRT1 decreased the abundance of EIF4A3 at the mRNAs of the EMT marker proteins N-cadherin and vimentin. Combined, our findings suggested that circ-SIRT1 regulates the expression of EMT-related proteins by preventing EIF4A3 recruitment to the respective mRNAs. Our results further indicate that circ-SIRT1 functions as an oncogene in CRC by promoting the proliferation, invasion, and EMT of CRC cells through the circ-SIRT1/EIF4A3/N-cadherin/vimentin pathway.
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spelling doaj-art-20cd09bf54d84df49a21b7b311abba7e2025-02-03T06:08:34ZengWileyAnalytical Cellular Pathology2210-71772210-71852021-01-01202110.1155/2021/57397695739769circ-SIRT1 Promotes Colorectal Cancer Proliferation and EMT by Recruiting and Binding to eIF4A3Xiangjie Wang0Shuang Liu1Bin Xu2Yabin Liu3Peng Kong4Changlin Li5Binghui Li6Department of General Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of General Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of General Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of General Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Biochemistry and Molecular Biology, Basic Medical College, Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Biochemistry and Molecular Biology, Basic Medical College, Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of General Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaCircular RNA (circRNA), a recently identified type of endogenous noncoding RNA, has been implicated in the occurrence and development of a variety of tumors; however, whether circ-SIRT1, derived from pre-mRNA of the parental SIRT1 gene, is involved in colorectal cancer (CRC) remains unknown, as do the potential underlying mechanisms. The expression of circ-SIRT1 in CRC cells and tissue was detected by RT-qPCR. Colony formation and Cell Counting Kit-8 assays were used to evaluate the effect of circ-SIRT1 knockdown on the proliferative ability of CRC cells. Wound healing and Transwell assays were used to assess the effect of circ-SIRT1 knockdown on the migratory and invasive capacity of CRC cells. RNA immunoprecipitation and RNA pull-down assays were employed to validate the binding of circ-SIRT1 to EIF4A3. Western blot was used to identify the changes in the expression of EIF4A3 and EMT-related proteins. The RT-qPCR results showed that circ-SIRT1 was highly expressed in CRC cells and tissue and was positively correlated with the depth of tumor invasion. Knocking down circ-SIRT1 inhibited the proliferation and invasion of CRC cells and EMT. We further found that EIF4A3 could bind to circ-SIRT1, and that overexpressing circ-SIRT1 decreased the abundance of EIF4A3 at the mRNAs of the EMT marker proteins N-cadherin and vimentin. Combined, our findings suggested that circ-SIRT1 regulates the expression of EMT-related proteins by preventing EIF4A3 recruitment to the respective mRNAs. Our results further indicate that circ-SIRT1 functions as an oncogene in CRC by promoting the proliferation, invasion, and EMT of CRC cells through the circ-SIRT1/EIF4A3/N-cadherin/vimentin pathway.http://dx.doi.org/10.1155/2021/5739769
spellingShingle Xiangjie Wang
Shuang Liu
Bin Xu
Yabin Liu
Peng Kong
Changlin Li
Binghui Li
circ-SIRT1 Promotes Colorectal Cancer Proliferation and EMT by Recruiting and Binding to eIF4A3
Analytical Cellular Pathology
title circ-SIRT1 Promotes Colorectal Cancer Proliferation and EMT by Recruiting and Binding to eIF4A3
title_full circ-SIRT1 Promotes Colorectal Cancer Proliferation and EMT by Recruiting and Binding to eIF4A3
title_fullStr circ-SIRT1 Promotes Colorectal Cancer Proliferation and EMT by Recruiting and Binding to eIF4A3
title_full_unstemmed circ-SIRT1 Promotes Colorectal Cancer Proliferation and EMT by Recruiting and Binding to eIF4A3
title_short circ-SIRT1 Promotes Colorectal Cancer Proliferation and EMT by Recruiting and Binding to eIF4A3
title_sort circ sirt1 promotes colorectal cancer proliferation and emt by recruiting and binding to eif4a3
url http://dx.doi.org/10.1155/2021/5739769
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