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Cited by 76MicroRNA in disease regulationProstate Cancer Treatment and ResearchCancer-related molecular mechanisms research

Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway

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Cai, Songwang, Chen, Ruihan, Li, Xiaojuan, Cai, Yi, Ye, Zhiqiang, Li, Shigeng, Li, Jun, Huang, Huaiqiu +11 more·2015·Oncotarget
DOI 10.18632/oncotarget.2880PMC PMC4414162
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Abstract

// Songwang Cai 1, * , Ruihan Chen 2, * , Xiaojuan Li 3 , Yi Cai 4 , Zhiqiang Ye 2 , Shigeng Li 2 , Jun Li 4 , Huaiqiu Huang 5 , Shubin Peng 4 , Jun Wang 4 , Yiran Tao 4 , Hongxing Huang 6 , Xinglai Wen 7 , Jianfeng Mo 7 , Zhupeng Deng 8 , Jian Wang 9 , Yangfan Zhang 4 , Xin Gao 4 , Xingqiao Wen 4 1 Department of Cardiothoracic Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 2 Department of Emergency, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 3 Department of Health Care, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 4 Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 5 Department of Dermatology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 6 Department of Urology, Zhongshan People's Hospital, Zhongshan City, Guangdong, China 7 Department of Urology, Qingyuan People's Hospital, Qingyuan City, Guangdong, China 8 Department of Urology, Taishan People's Hospital, Taishan City, Guangdong, China 9 Department of Urology, The First People's Hospital of Foshan City, Foshan City, Guangdong, China * These authors have contributed equally to this work Correspondence to: Xingqiao Wen, e-mail: wenxq@mail.sysu.edu.cn Keywords: microRNA, miR23a, prostate cancer, metastasis, cytoskeleton Received: August 12, 2014 Accepted: December 08, 2014 Published: February 24, 2015 ABSTRACT Here we found that levels of miR-23a were decreased in prostate cancer cell lines and tumor tissues. These low levels were associated with poor patients’ prognosis. MiR-23a inhibited migration and invasion of prostate cancer in vivo and in orthotopic prostate cancer mice model. MiR-23a decreased levels of p21-activated kinase 6 (PAK6). Expression of miR-23a inhibited phosphorylation of LIM kinase 1 (LIMK1) and cofilin, in turn suppressing formation of stress fibers and actin filaments, which was required for cell motility and invasion. PAK6 bound to LIMK1 and activated it via phosphorylation at Thr-508. Also, PAK6 and LIMK1 were colocalized in the cytoplasma. Thus, miR-23a regulated cytoskeleton by affecting LIMK1 and cofilin. In summary, we have identified the miR-23a-PAK6-LIMK1 pathway of prostate cancer metastasis. Potential therapeutic approach by targeting miR-23 is suggested.

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  • Expression level of miR-23a displayed an abnormal decrease in prostate cancer cell lines, opposite to breast and ovarian cancers.

    “The expression level of miR-23a displayed an abnormal decrease in this cancer cell lines, which is opposite to we mentioned previously in breast and ovarian cancers [88].”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [88]

  • miR-23a can regulate the PAK6-LIMK1 signaling pathway in prostate cancer, significantly inhibiting cell migration and invasion.

    “miR-23a can regulate the PAK6-LIMK1 signaling pathway in prostate cancer, thereby significantly inhibiting cell migration and invasion.”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [88]

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References 43 · Cited by 76

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Authors
Cai, S., Chen, R., Li, X., Cai, Y., Ye, Z., Li, S., Li, J., Huang, H., Peng, S., Wang, J., Tao, Y., Huang, H., Wen, X., Mo, J., Deng, Z., Wang, J., Zhang, Y., Gao, X., & Wen, X.
Affiliations
  • Sun Yat-sen University (CN)
  • Department of Urology, Qingyuan People's Hospital, Qingyuan City, Guangdong, China
  • Department of Urology, Taishan People's Hospital, Taishan City, Guangdong, China
Corresponding author
  • Cai, Songwang
  • Chen, Ruihan
ORCID
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2015-01-16
Volume
6
Issue
6
Pages
3904-3917
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.2880
PMC
PMC4414162
OpenAlex
W1558158633
Cited by
76
References
43
Citations by year
2026: 1 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 6 · 2020: 9 · 2019: 8 · 2018: 10 · 2017: 12 · 2016: 14 · 2015: 3
FWCI
4.30
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81372767, 81072115, 30901768)
  • Sun Yat-sen University
  • Program for New Century Excellent Talents in University (NCET-11-)
  • Fundamental Research Funds for the Central Universities
  • Science and Technology Planning Project of Guangdong Province (2012B031800063, 2013B021800183)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
prostate cancer, metastasis, PAK6, LIMK1, p21-activated kinase, LIM kinase, cytoskeleton, cell migration, cell invasion, prognosis, microRNA downregulation, orthotopic mouse model, tumor suppressor microRNA, prognostic factors, metastasis biomarkers, cell cycle arrest, apoptosis, cell proliferation, cell adhesion
MeSH terms
Aged, Animals, Humans, Male, Mice, Nude, Neoplasm Metastasis, Prostatic Neoplasms, Signal Transduction, Down-Regulation, Gene Expression Profiling, MicroRNAs, Cell Line, Tumor, Mice, Lim Kinases, p21-Activated Kinases, HEK293 Cells, Heterografts

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