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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
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