Cargando…
MiR‐326/Sp1/KLF3: A novel regulatory axis in lung cancer progression
OBJECTIVES: To investigate the function and regulatory mechanism of Krüppel‐like factor 3 (KLF3) in lung cancer. MATERIALS AND METHODS: KLF3 expression was analysed by qRT‐PCR and Western blot assays. The proliferation, migration, invasion, cycle and apoptosis were measured by CCK‐8 and EdU, wound‐h...
Autores principales: | , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495967/ https://www.ncbi.nlm.nih.gov/pubmed/30485570 http://dx.doi.org/10.1111/cpr.12551 |
_version_ | 1783415380144816128 |
---|---|
author | Wang, Rong Xu, Jiali Xu, Jing Zhu, Wei Qiu, Tianzhu Li, Jun Zhang, Meiling Wang, Qianqian Xu, Tongpeng Guo, Renhua Lu, Kaihua Yin, Yongmei Gu, Yanhong Zhu, Lingjun Huang, Puwen Liu, Ping Liu, Lianke De, Wei Shu, Yongqian |
author_facet | Wang, Rong Xu, Jiali Xu, Jing Zhu, Wei Qiu, Tianzhu Li, Jun Zhang, Meiling Wang, Qianqian Xu, Tongpeng Guo, Renhua Lu, Kaihua Yin, Yongmei Gu, Yanhong Zhu, Lingjun Huang, Puwen Liu, Ping Liu, Lianke De, Wei Shu, Yongqian |
author_sort | Wang, Rong |
collection | PubMed |
description | OBJECTIVES: To investigate the function and regulatory mechanism of Krüppel‐like factor 3 (KLF3) in lung cancer. MATERIALS AND METHODS: KLF3 expression was analysed by qRT‐PCR and Western blot assays. The proliferation, migration, invasion, cycle and apoptosis were measured by CCK‐8 and EdU, wound‐healing and Transwell, and flow cytometry assays. The tumour growth was detected by nude mouse tumorigenesis assay. In addition, the interaction between KLF3 and Sp1 was accessed by luciferase reporter, EMSA and ChIP assay. JAK2, STAT3, PI3K and p‐AKT levels were evaluated by Western blot and IHC assays. RESULTS: The results indicated that KLF3 expression was elevated in lung cancer tissues. Knockdown of KLF3 inhibited lung cancer cell proliferation, migration and invasion, and induced cell cycle arrest and apoptosis. In addition, the downregulation of KLF3 suppressed tumour growth in vivo. KLF3 was transcriptionally activated by Sp1. miR‐326 could bind to 3′UTR of Sp1 but not KLF3 and decreased the accumulation of Sp1, which further indirectly reduced KLF3 expression and inactivated JAK2/STAT3 and PI3K/AKT signaling pathways in vitro and in vivo. CONCLUSIONS: Our data demonstrate that miR‐326/Sp1/KLF3 regulatory axis is involved in the development of lung cancer, which hints the potential target for the further therapeutic strategy against lung cancer. |
format | Online Article Text |
id | pubmed-6495967 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64959672020-03-13 MiR‐326/Sp1/KLF3: A novel regulatory axis in lung cancer progression Wang, Rong Xu, Jiali Xu, Jing Zhu, Wei Qiu, Tianzhu Li, Jun Zhang, Meiling Wang, Qianqian Xu, Tongpeng Guo, Renhua Lu, Kaihua Yin, Yongmei Gu, Yanhong Zhu, Lingjun Huang, Puwen Liu, Ping Liu, Lianke De, Wei Shu, Yongqian Cell Prolif Original Articles OBJECTIVES: To investigate the function and regulatory mechanism of Krüppel‐like factor 3 (KLF3) in lung cancer. MATERIALS AND METHODS: KLF3 expression was analysed by qRT‐PCR and Western blot assays. The proliferation, migration, invasion, cycle and apoptosis were measured by CCK‐8 and EdU, wound‐healing and Transwell, and flow cytometry assays. The tumour growth was detected by nude mouse tumorigenesis assay. In addition, the interaction between KLF3 and Sp1 was accessed by luciferase reporter, EMSA and ChIP assay. JAK2, STAT3, PI3K and p‐AKT levels were evaluated by Western blot and IHC assays. RESULTS: The results indicated that KLF3 expression was elevated in lung cancer tissues. Knockdown of KLF3 inhibited lung cancer cell proliferation, migration and invasion, and induced cell cycle arrest and apoptosis. In addition, the downregulation of KLF3 suppressed tumour growth in vivo. KLF3 was transcriptionally activated by Sp1. miR‐326 could bind to 3′UTR of Sp1 but not KLF3 and decreased the accumulation of Sp1, which further indirectly reduced KLF3 expression and inactivated JAK2/STAT3 and PI3K/AKT signaling pathways in vitro and in vivo. CONCLUSIONS: Our data demonstrate that miR‐326/Sp1/KLF3 regulatory axis is involved in the development of lung cancer, which hints the potential target for the further therapeutic strategy against lung cancer. John Wiley and Sons Inc. 2018-11-28 /pmc/articles/PMC6495967/ /pubmed/30485570 http://dx.doi.org/10.1111/cpr.12551 Text en © 2018 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Wang, Rong Xu, Jiali Xu, Jing Zhu, Wei Qiu, Tianzhu Li, Jun Zhang, Meiling Wang, Qianqian Xu, Tongpeng Guo, Renhua Lu, Kaihua Yin, Yongmei Gu, Yanhong Zhu, Lingjun Huang, Puwen Liu, Ping Liu, Lianke De, Wei Shu, Yongqian MiR‐326/Sp1/KLF3: A novel regulatory axis in lung cancer progression |
title | MiR‐326/Sp1/KLF3: A novel regulatory axis in lung cancer progression |
title_full | MiR‐326/Sp1/KLF3: A novel regulatory axis in lung cancer progression |
title_fullStr | MiR‐326/Sp1/KLF3: A novel regulatory axis in lung cancer progression |
title_full_unstemmed | MiR‐326/Sp1/KLF3: A novel regulatory axis in lung cancer progression |
title_short | MiR‐326/Sp1/KLF3: A novel regulatory axis in lung cancer progression |
title_sort | mir‐326/sp1/klf3: a novel regulatory axis in lung cancer progression |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495967/ https://www.ncbi.nlm.nih.gov/pubmed/30485570 http://dx.doi.org/10.1111/cpr.12551 |
work_keys_str_mv | AT wangrong mir326sp1klf3anovelregulatoryaxisinlungcancerprogression AT xujiali mir326sp1klf3anovelregulatoryaxisinlungcancerprogression AT xujing mir326sp1klf3anovelregulatoryaxisinlungcancerprogression AT zhuwei mir326sp1klf3anovelregulatoryaxisinlungcancerprogression AT qiutianzhu mir326sp1klf3anovelregulatoryaxisinlungcancerprogression AT lijun mir326sp1klf3anovelregulatoryaxisinlungcancerprogression AT zhangmeiling mir326sp1klf3anovelregulatoryaxisinlungcancerprogression AT wangqianqian mir326sp1klf3anovelregulatoryaxisinlungcancerprogression AT xutongpeng mir326sp1klf3anovelregulatoryaxisinlungcancerprogression AT guorenhua mir326sp1klf3anovelregulatoryaxisinlungcancerprogression AT lukaihua mir326sp1klf3anovelregulatoryaxisinlungcancerprogression AT yinyongmei mir326sp1klf3anovelregulatoryaxisinlungcancerprogression AT guyanhong mir326sp1klf3anovelregulatoryaxisinlungcancerprogression AT zhulingjun mir326sp1klf3anovelregulatoryaxisinlungcancerprogression AT huangpuwen mir326sp1klf3anovelregulatoryaxisinlungcancerprogression AT liuping mir326sp1klf3anovelregulatoryaxisinlungcancerprogression AT liulianke mir326sp1klf3anovelregulatoryaxisinlungcancerprogression AT dewei mir326sp1klf3anovelregulatoryaxisinlungcancerprogression AT shuyongqian mir326sp1klf3anovelregulatoryaxisinlungcancerprogression |