Skip to main content
Erschienen in: Clinical and Translational Oncology 1/2021

29.05.2020 | Research Article

Effect of shRNA-mediated regulation of S100A4 gene expression on proliferation and apoptosis of KLE endometrial cancer cells

verfasst von: W. Ren, Y. B. Chi, J. L. Sun

Erschienen in: Clinical and Translational Oncology | Ausgabe 1/2021

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To investigate the effect of shRNA-regulated S100A4 expression on the proliferation and apoptosis in KLE endometrial cancer cells.

Methods

S100A4-OVER and S100A4-shRNA were transfected into KLE endometrial cancer cells using lentiviral sh-RNA technology. Passive OVER-NC cell line and shRNA-NC cell line were used as a negative control group and non-transfected Control cell line as a blank control group. After 48 h of transfection, the expressions of S100A4 and protein were detected by real-time fluorescence quantitative PCR and Western blotting, respectively. CCK-8 detection and flow cytometer were used to detect cell proliferation and apoptosis, respectively.

Results

Compared with the normal control group and the negative control group, the transfection efficiency and shRNA targeting of the shRNA-interfered S100A4 gene were verified at the levels of mRNA and protein expression. The expression of the disrupted S100A4 gene at S100A4 mRNA and protein levels in endometrial cancer cells was determined. The proliferation efficiency of KLE cells in S100A4-OVER group was significantly higher than that in other four groups; the proliferation rate of S100A4-shRNA cells decreased slightly;, the apoptotic rate of KLE cells in S100A4-shRNA group increased significantly, and the apoptotic rate of KLE cells in S100A4-OVER group decreased compared with NC group.

Conclusion

Specific regulation of S100A4 gene expression:, the enhanced expression of the S100A4 gene may promote the proliferation of KLE endometrial cancer cells; the inhibited expression of the S100A4 gene may promote the apoptosis of KLE endometrial cancer cells. S100A4 expression is closely related to the biological characteristics of endometrial cancer.
Literatur
2.
Zurück zum Zitat Donato R, Cannon BR, Sorci G, et al. Functions of S100 proteins. Curr Mol Med. 2013;13:24–57.CrossRef Donato R, Cannon BR, Sorci G, et al. Functions of S100 proteins. Curr Mol Med. 2013;13:24–57.CrossRef
3.
Zurück zum Zitat Ismail NI, Kaur G, Hashim H, Hassan MS. S100A4 over-expression proves to be independent marker for breast cancer progression. Cancer Cell Int. 2008;8:12.CrossRef Ismail NI, Kaur G, Hashim H, Hassan MS. S100A4 over-expression proves to be independent marker for breast cancer progression. Cancer Cell Int. 2008;8:12.CrossRef
4.
Zurück zum Zitat Wang YY, Ye ZY, Zhao ZS, et al. High-level expression of S100A4 correlates with lymph node metastasis and poor prognosis in patients with gastric cancer. Ann Surg Oncol. 2010;17:89–97.CrossRef Wang YY, Ye ZY, Zhao ZS, et al. High-level expression of S100A4 correlates with lymph node metastasis and poor prognosis in patients with gastric cancer. Ann Surg Oncol. 2010;17:89–97.CrossRef
5.
Zurück zum Zitat Kwak JM, Lee HJ, Kim SH, et al. Expression of protein S100A4 is a predictor of recurrence in colorectal cancer. World J Gastroenterol. 2010;16:3897–904.CrossRef Kwak JM, Lee HJ, Kim SH, et al. Expression of protein S100A4 is a predictor of recurrence in colorectal cancer. World J Gastroenterol. 2010;16:3897–904.CrossRef
6.
Zurück zum Zitat Min HS, Choe G, Kim SW, et al. S100A4 expression is associated with lymph node metastasis in papillary microcarcinoma of the thyroid. Mod Pathol. 2008;21:748–55.CrossRef Min HS, Choe G, Kim SW, et al. S100A4 expression is associated with lymph node metastasis in papillary microcarcinoma of the thyroid. Mod Pathol. 2008;21:748–55.CrossRef
7.
Zurück zum Zitat Tsuna M, Kageyama SI, Fukuoka J, et al. Significance of S100A4 as a prognostic marker of lung squamous cell carcinoma. Anticancer Res. 2009;29:2547–54.PubMed Tsuna M, Kageyama SI, Fukuoka J, et al. Significance of S100A4 as a prognostic marker of lung squamous cell carcinoma. Anticancer Res. 2009;29:2547–54.PubMed
8.
Zurück zum Zitat Davies BR, O'Donnell M, Durkan GC, et al. Expression of SI00A4 protein is associated with metastasis and reduced survival in human bladder cancer. J Pathol. 2002;196:292–9.CrossRef Davies BR, O'Donnell M, Durkan GC, et al. Expression of SI00A4 protein is associated with metastasis and reduced survival in human bladder cancer. J Pathol. 2002;196:292–9.CrossRef
9.
Zurück zum Zitat Kikuchi N, Horiuchi A, Osada R, et al. Nuclear expression of S100A4 is associated with aggressive behavior of epithelial ovarian carcinoma: an important autocrine/paracrine factor in tumor progression. Cancer Sci. 2006;97:1061–9.CrossRef Kikuchi N, Horiuchi A, Osada R, et al. Nuclear expression of S100A4 is associated with aggressive behavior of epithelial ovarian carcinoma: an important autocrine/paracrine factor in tumor progression. Cancer Sci. 2006;97:1061–9.CrossRef
10.
Zurück zum Zitat Chong H, Lee J, Yoon M, et al. Prognostic value of cytoplasmic expression of S100A4 protein in endometrial carcinoma. Oncol Rep. 2014;31:2701–7.CrossRef Chong H, Lee J, Yoon M, et al. Prognostic value of cytoplasmic expression of S100A4 protein in endometrial carcinoma. Oncol Rep. 2014;31:2701–7.CrossRef
11.
Zurück zum Zitat Donato R. S100: a multigenic family of calci-um-modulated proteins of the EF-hand type with intracellular and extracellular unctional roles. Int J Biochem Cell Biol. 2001;33:637–68.CrossRef Donato R. S100: a multigenic family of calci-um-modulated proteins of the EF-hand type with intracellular and extracellular unctional roles. Int J Biochem Cell Biol. 2001;33:637–68.CrossRef
12.
Zurück zum Zitat Heizmann CW, Fritz G, Schafer BW. S100 proteins: structure, functions and pathology. Front Biosci. 2002;7:d1356–1368.PubMed Heizmann CW, Fritz G, Schafer BW. S100 proteins: structure, functions and pathology. Front Biosci. 2002;7:d1356–1368.PubMed
13.
Zurück zum Zitat Boye K, Maelandsmo GM. S100A4 and metastasis: a small actor playing many roles. Am J Pathol. 2010;176:528–35.CrossRef Boye K, Maelandsmo GM. S100A4 and metastasis: a small actor playing many roles. Am J Pathol. 2010;176:528–35.CrossRef
14.
Zurück zum Zitat Mylona E, Giannopoulou I, Fasomytakis E, Nomikos A, Magkou C, Bakarakos P, Nakopoulou L. The clinicopathologic and prognostic significance of CD44+/CD24(−/low) and CD44−/CD24+ tumor cells in invasive breast carcinomas. Hum Pathol. 2008;7:1096–102.CrossRef Mylona E, Giannopoulou I, Fasomytakis E, Nomikos A, Magkou C, Bakarakos P, Nakopoulou L. The clinicopathologic and prognostic significance of CD44+/CD24(−/low) and CD44−/CD24+ tumor cells in invasive breast carcinomas. Hum Pathol. 2008;7:1096–102.CrossRef
15.
Zurück zum Zitat Liu J, Fu S, Xu Y, Zheng Z. RNA interference targeting inhibition of S100A4 suppresses cell growth and promotes apoptosis in human laryngeal carcinoma Hep-2 cells. Mol Med Rep. 2014;3:1389–94.CrossRef Liu J, Fu S, Xu Y, Zheng Z. RNA interference targeting inhibition of S100A4 suppresses cell growth and promotes apoptosis in human laryngeal carcinoma Hep-2 cells. Mol Med Rep. 2014;3:1389–94.CrossRef
16.
Zurück zum Zitat Egeland EV, Boye K, Park D, Synnestvedt M, Sauer T, Oslo Breast Cancer Consortium (OSBREAC), Naume B, Borgen E, Mælandsmo GM. Prognostic significance of S100A4-ex-pression and subcellular localization in early-stage breast cancer. Breast Cancer Res Treat. 2017;162:127–37.CrossRef Egeland EV, Boye K, Park D, Synnestvedt M, Sauer T, Oslo Breast Cancer Consortium (OSBREAC), Naume B, Borgen E, Mælandsmo GM. Prognostic significance of S100A4-ex-pression and subcellular localization in early-stage breast cancer. Breast Cancer Res Treat. 2017;162:127–37.CrossRef
17.
Zurück zum Zitat Wang H, Shi J, Luo Y, Liao Q, Niu Y, Zhang F, Shao Z, Ding Y, Zhao L. LIM and SH3 protein 1 induces TGFβ-mediated epithelial-mesenchymal transition in human colorectal cancer by regulating S100A4 expression. Clin Cancer Res. 2014;22:5835–47.CrossRef Wang H, Shi J, Luo Y, Liao Q, Niu Y, Zhang F, Shao Z, Ding Y, Zhao L. LIM and SH3 protein 1 induces TGFβ-mediated epithelial-mesenchymal transition in human colorectal cancer by regulating S100A4 expression. Clin Cancer Res. 2014;22:5835–47.CrossRef
18.
Zurück zum Zitat Wang XG, Meng Q, Qi FM, Yang QF. Blocking TGF-13 inhibits breast cancer cell invasiveness via ERK/S100A4 signal. Eur Rev Med Pharmacol Sci. 2014;18:3844–53.PubMed Wang XG, Meng Q, Qi FM, Yang QF. Blocking TGF-13 inhibits breast cancer cell invasiveness via ERK/S100A4 signal. Eur Rev Med Pharmacol Sci. 2014;18:3844–53.PubMed
19.
Zurück zum Zitat Xu X, Su B, Xie C, Wei S, Zhou Y, Liu H, Dai W, Cheng P, Wang F, Xu X, Guo C. Sonic Hedgehog-Glil signaling path—way regulates the epithelial mesenehymal transition (EMT) by me-diating a new target gene, S100A4, in pancreatic cancer cells. PLoS ONE. 2014;9:e96441.CrossRef Xu X, Su B, Xie C, Wei S, Zhou Y, Liu H, Dai W, Cheng P, Wang F, Xu X, Guo C. Sonic Hedgehog-Glil signaling path—way regulates the epithelial mesenehymal transition (EMT) by me-diating a new target gene, S100A4, in pancreatic cancer cells. PLoS ONE. 2014;9:e96441.CrossRef
20.
Zurück zum Zitat Küper C, Beck FX, Neohofer W. NFAT5-mediated expression of S100A4 contributes to proliferation and migration of renal carcino-ma cells. Front Physiol. 2014;5:293.CrossRef Küper C, Beck FX, Neohofer W. NFAT5-mediated expression of S100A4 contributes to proliferation and migration of renal carcino-ma cells. Front Physiol. 2014;5:293.CrossRef
21.
Zurück zum Zitat Hua J, Chen D, Fu H, Zhang R, Shen W, Liu S, Sun K, Sun X. Short hairpin RNA·mediated inhibition of S100A4 promotes apoptosis and suppresses proliferation of BGC823 gastric cancer cells in vitro and in vivo. Cancer Lett. 2010;292:41–7.CrossRef Hua J, Chen D, Fu H, Zhang R, Shen W, Liu S, Sun K, Sun X. Short hairpin RNA·mediated inhibition of S100A4 promotes apoptosis and suppresses proliferation of BGC823 gastric cancer cells in vitro and in vivo. Cancer Lett. 2010;292:41–7.CrossRef
22.
Zurück zum Zitat Liu J, Fu S, Xu Y, Zheng Z. RNA interference targeting inhibition of S100A4 suppresses cell growth and promotes apoptosis in human laryngeal carcinoma Hep 2 cells. Mol Med Rep. 2014;10:1389–94.CrossRef Liu J, Fu S, Xu Y, Zheng Z. RNA interference targeting inhibition of S100A4 suppresses cell growth and promotes apoptosis in human laryngeal carcinoma Hep 2 cells. Mol Med Rep. 2014;10:1389–94.CrossRef
23.
Zurück zum Zitat Yang XC, Wang X, Luo L, Dong DH, Yu QC, Wang XS, Zhao K. RNA interference suppression of A100A4 reduces the growth and metastatic phenotype of human renal cancer cells via NF-kB-dependent MMP-2 and bcl-2pathway. Eur Rev Med Pharmacol Sci. 2013;17:1669–800.PubMed Yang XC, Wang X, Luo L, Dong DH, Yu QC, Wang XS, Zhao K. RNA interference suppression of A100A4 reduces the growth and metastatic phenotype of human renal cancer cells via NF-kB-dependent MMP-2 and bcl-2pathway. Eur Rev Med Pharmacol Sci. 2013;17:1669–800.PubMed
24.
Zurück zum Zitat Ma L, Wu AG, Ji SF, Yang HF. Effect of short hairpin RNA-targeted S100A4 on proliferation of breast cancer MCF-7 cells. Chin PLA Postgrad Med Sch. 2010;31:63–6. Ma L, Wu AG, Ji SF, Yang HF. Effect of short hairpin RNA-targeted S100A4 on proliferation of breast cancer MCF-7 cells. Chin PLA Postgrad Med Sch. 2010;31:63–6.
25.
Zurück zum Zitat Mahon PC, Baril P, Bhakta V, Chelala C, Caulee K, Harada T, Lemoine NR. S100A4 contributes to the suppres-sion of BNIP3 expression, chemoresistance, and inhibition of apoptosis in pancreatic cancer. Cancer Res. 2007;67:6786–95.CrossRef Mahon PC, Baril P, Bhakta V, Chelala C, Caulee K, Harada T, Lemoine NR. S100A4 contributes to the suppres-sion of BNIP3 expression, chemoresistance, and inhibition of apoptosis in pancreatic cancer. Cancer Res. 2007;67:6786–95.CrossRef
26.
Zurück zum Zitat Li Q, Dai C, Xue R, Wang P, Chen L, Han Y, Erben U, Qin Z. S100A4 protects myeloid-derived suppressor cells from intrinsic apoptosis via TLR4-ERK1/2 signaling. Front Immunol. 2018;9:388.CrossRef Li Q, Dai C, Xue R, Wang P, Chen L, Han Y, Erben U, Qin Z. S100A4 protects myeloid-derived suppressor cells from intrinsic apoptosis via TLR4-ERK1/2 signaling. Front Immunol. 2018;9:388.CrossRef
27.
Zurück zum Zitat Grigorian M, Lukanidin E. Activator of me-tastasis in cancer cells, Mst1/S100A4 protein binds to tumor suppressor protein p53. Genetika. 2003;39:900–8.PubMed Grigorian M, Lukanidin E. Activator of me-tastasis in cancer cells, Mst1/S100A4 protein binds to tumor suppressor protein p53. Genetika. 2003;39:900–8.PubMed
28.
Zurück zum Zitat Orre LM, Panizza E, Kaminskyy VO, Vernet E, Gräslund T, Zhivotovsky B, Lehtiö J. S100A4 interacts with p53 in the nucleus and promotes p53 degradation. Oncogene. 2013;32:5531–40.CrossRef Orre LM, Panizza E, Kaminskyy VO, Vernet E, Gräslund T, Zhivotovsky B, Lehtiö J. S100A4 interacts with p53 in the nucleus and promotes p53 degradation. Oncogene. 2013;32:5531–40.CrossRef
Metadaten
Titel
Effect of shRNA-mediated regulation of S100A4 gene expression on proliferation and apoptosis of KLE endometrial cancer cells
verfasst von
W. Ren
Y. B. Chi
J. L. Sun
Publikationsdatum
29.05.2020
Verlag
Springer International Publishing
Erschienen in
Clinical and Translational Oncology / Ausgabe 1/2021
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-020-02406-7

Weitere Artikel der Ausgabe 1/2021

Clinical and Translational Oncology 1/2021 Zur Ausgabe

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

CUP-Syndrom: Künstliche Intelligenz kann Primärtumor finden

30.04.2024 Künstliche Intelligenz Nachrichten

Krebserkrankungen unbekannten Ursprungs (CUP) sind eine diagnostische Herausforderung. KI-Systeme können Pathologen dabei unterstützen, zytologische Bilder zu interpretieren, um den Primärtumor zu lokalisieren.

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.