Clusterin silencing inhibits proliferation and reduces invasion in human laryngeal squamous carcinoma cells
Open accessAbstract
BACKGROUND: Clusterin is, in its major form, a secreted heterodimeric disulfide-linked glycoprotein (sCLU), which plays important roles in cell survival and death. In laryngeal squamous cell carcinomas (LSCC), sCLU is up-regulated and its expression is related to the invasiveness of these tumors. The purpose of this study was to explore the inhibiting role of sCLU gene silence in the invasive ability and growth of Hep-2 human laryngeal squamous carcinoma cells (Hep-2) by transfection of short hairpin RNA expression plasmids against sCLU (sCLU-shRNA) (in vivo) or small interference RNA (sCLU-siRNA) (in vitro). METHODS: sCLU-siRNA and the control siRNA were transfected into Hep-2 cells using Lipofectamine 2000. RT-PCR and Western blot were used to detect the effect of siRNA transfection on sCLU mRNA and sCLU protein expression. The invasive activity of sCLU-siRNA-transfected Hep-2 cells was measured with the modified Boyden chamber assay and wound healing assay. The effects of sCLU-siRNA on cell proliferation were evaluated by MTT assay. Apoptosis was measured by Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double-staining methods. We next evaluated the effects of sCLU silencing by sCLU-shRNA transfection in vivo on tumor growth and metastatic properties to the lung. Terminal deoxytransferase-mediated dUTP nick end labeling (TUNEL) staining was used to observe the apoptosis in the xenografts. RESULTS: It showed that siRNA-mediated down-regulation of sCLU expression in Hep-2 cells significantly inhibited cell proliferation and promoted apoptosis in vitro. Furthermore, siRNA-mediated down-regulation of sCLU expression decreases in vitro cell migration and invasion ability. In vivo, the average volume of tumors in the sCLU-shRNA transfected group was significantly lower than in the control group (P<0.01), and the significant apoptosis detected with TUNEL was indicated in the sCLU-shRNA transfected groups (P<0.05). Significantly, we found that sCLU-shRNA could exert marked inhibition of the lung metastasis of Hep-2 cells in nude mice in vivo. CONCLUSIONS: sCLU gene silence can inhibit invasion and growth of LSCC. sCLU may provide a potential therapeutic target against human LSCC.
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Clusterin is involved in apoptosis, cell proliferation, and clearance of misfolded proteins.
“Clusterin (CLU), a multifunctional glycoprotein also known as apolipoprotein J, plays a role in several cellular processes including apoptosis, proliferation, and clearance of misfolded proteins (Kim and Choi, 2011,Wang, et al., 2014,Wyatt, et al., 2011)”
From A potential endophenotype for Alzheimer's disease: cerebrospinal fluid clusterin (2016) · cites this paper as Wang, et al., 2014
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- Authors
- Wang, Q., Cao, W., Su, Q., Liu, Z., & Zhang, L.
- Affiliations
- Linyi People's Hospital (CN)
- Affiliated Hospital of Qingdao University (CN)
- Corresponding author
- Zhang, Lin
- Venue
- World Journal of Surgical Oncology
- Published
- 2014-04-26
- Volume
- 12
- Issue
- 1
- Pages
- 124-124
- ISSN
- 1477-7819 (ISSN-L)
- PMC
- PMC4016627
- OpenAlex
- W2127824254
- Cited by
- 14
- References
- 28
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 4 · 2020: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- World Journal of Surgical Oncology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Clusterin in disease pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- clusterin, laryngeal squamous cell carcinoma, gene silencing, siRNA, shRNA, cell proliferation, tumor invasion, apoptosis, lung metastasis, HEp-2 cells, therapeutic target, metastasis suppression, tumor growth inhibition, xenografts, cell migration
- MeSH terms
- Animals, Carcinoma, Squamous Cell, Cell Adhesion, Cell Movement, Female, Humans, Laryngeal Neoplasms, Lung Neoplasms, Neoplasm Invasiveness, RNA, Messenger, Tumor Cells, Cultured, Wound Healing, Blotting, Western, Mice, SCID, Apoptosis, Reverse Transcriptase Polymerase Chain Reaction, Gene Silencing, RNA, Small Interfering, Cell Proliferation, Clusterin, Mice, Real-Time Polymerase Chain Reaction
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