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Overexpression of proteasomal activator PA28α serves as a prognostic factor in oral squamous cell carcinoma.

Feng X, Jiang Y, Xie L, Jiang L, Li J, Sun C, Xu H, Wang R, Zhou M, Zhou Y, Dan H, Wang Z, Ji N, Deng P, Liao G, Geng N, Wang Y, Zhang D, Lin Y, Ye L, Liang X, Li L, Luo G, Feng M, Fang J, Zeng X, Wang Z, Chen Q - J. Exp. Clin. Cancer Res. (2016)

Bottom Line: PA28α was found to be overexpressed in OSCC cell lines and tumor tissues.Specific knockdown of PA28α inhibited OSCC cell proliferation, migration, invasion in vitro and reduced the growth of OSCC xenografts in vivo.These results suggest that PA28α is involved in OSCC oncogenesis and may serve as a potential prognostic factor.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Sec.3, Renminnan Road, Chengdu, Sichuan, 610041, China. fengxiaodong84@126.com.

ABSTRACT

Background: Despite recent advances in oral squamous cell carcinoma (OSCC) diagnosis and therapy, disease recurrence remains common and is strongly associated with mortality. It is therefore critical to identify new targets for both treatment and diagnostic purposes. We aimed at investigating the role of PA28α, a proteasomal activator in OSCC.

Methods: The expression of PA28α was examined in a panel of OSCC cell lines and tissues, associated with oncomine analysis. In a large OSCC patient cohort, the prognostic value of PA28α expression was evaluated. Primary clinical end points were recurrence-free and overall survival rate. Functional involvement of PA28α in OSCC was examined in both in vitro and in vivo models upon specific siRNA knockdown.

Results: PA28α was found to be overexpressed in OSCC cell lines and tumor tissues. High expression of PA28α was significantly associated with recurrence and poorer overall survival. Specific knockdown of PA28α inhibited OSCC cell proliferation, migration, invasion in vitro and reduced the growth of OSCC xenografts in vivo. Multivariate Cox regression analyses revealed PA28α as independent prognostic predictors.

Conclusions: These results suggest that PA28α is involved in OSCC oncogenesis and may serve as a potential prognostic factor.

No MeSH data available.


Related in: MedlinePlus

PA28α knockdown in CAL27 and HSC3 inhibits cell growth, but doesn’t induce apoptosis in vitro. a PA28α was knocked down by siRNA targeting PA28α, illustrated by Western blotting. b MTT assay, PA28α silencing in CAL27 and HSC3 inhibits cell growth. c Clonogenic assay, PA28α silencing in CAL27 and HSC3 inhibits clonogenic. d Edu assay, PA28α silencing in CAL27 and HSC3 inhibits proliferation. e TUNEL assay, PA28α silencing in CAL27 and HSC3 has no effect on apoptosis. PA28α overexpression in OSCC cell lines promotes cell proliferation in vitro was indicated in Additional file 8: Figure S5. Data are reported as means ± SEM for three independantly experiments. (ANOVA or T test, *p < 0.05, ** p < 0.01, *** p < 0.001)
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Fig3: PA28α knockdown in CAL27 and HSC3 inhibits cell growth, but doesn’t induce apoptosis in vitro. a PA28α was knocked down by siRNA targeting PA28α, illustrated by Western blotting. b MTT assay, PA28α silencing in CAL27 and HSC3 inhibits cell growth. c Clonogenic assay, PA28α silencing in CAL27 and HSC3 inhibits clonogenic. d Edu assay, PA28α silencing in CAL27 and HSC3 inhibits proliferation. e TUNEL assay, PA28α silencing in CAL27 and HSC3 has no effect on apoptosis. PA28α overexpression in OSCC cell lines promotes cell proliferation in vitro was indicated in Additional file 8: Figure S5. Data are reported as means ± SEM for three independantly experiments. (ANOVA or T test, *p < 0.05, ** p < 0.01, *** p < 0.001)

Mentions: Three PA28α targeting siRNAs were designed to downregulate PA28α expression. Two PA28α overexpressing OSCC cell lines, CAL27 and HSC3, were transfected with the most effective siRNA-PA28α while PA28 β and γ weren't affected (Additional file 7: Figure S4), following with tests of cells and subjected to MTT, colony formation, Edu coporation assay and TUNEL assay. PA28 knockdown (Fig. 3a) in CAL27 and HSC3 decreased cells viability, colony formation and cells proliferation (Fig. 3b, c, d), but no effects on apoptosis of these cells (Fig. 3e).Fig. 3


Overexpression of proteasomal activator PA28α serves as a prognostic factor in oral squamous cell carcinoma.

Feng X, Jiang Y, Xie L, Jiang L, Li J, Sun C, Xu H, Wang R, Zhou M, Zhou Y, Dan H, Wang Z, Ji N, Deng P, Liao G, Geng N, Wang Y, Zhang D, Lin Y, Ye L, Liang X, Li L, Luo G, Feng M, Fang J, Zeng X, Wang Z, Chen Q - J. Exp. Clin. Cancer Res. (2016)

PA28α knockdown in CAL27 and HSC3 inhibits cell growth, but doesn’t induce apoptosis in vitro. a PA28α was knocked down by siRNA targeting PA28α, illustrated by Western blotting. b MTT assay, PA28α silencing in CAL27 and HSC3 inhibits cell growth. c Clonogenic assay, PA28α silencing in CAL27 and HSC3 inhibits clonogenic. d Edu assay, PA28α silencing in CAL27 and HSC3 inhibits proliferation. e TUNEL assay, PA28α silencing in CAL27 and HSC3 has no effect on apoptosis. PA28α overexpression in OSCC cell lines promotes cell proliferation in vitro was indicated in Additional file 8: Figure S5. Data are reported as means ± SEM for three independantly experiments. (ANOVA or T test, *p < 0.05, ** p < 0.01, *** p < 0.001)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4759779&req=5

Fig3: PA28α knockdown in CAL27 and HSC3 inhibits cell growth, but doesn’t induce apoptosis in vitro. a PA28α was knocked down by siRNA targeting PA28α, illustrated by Western blotting. b MTT assay, PA28α silencing in CAL27 and HSC3 inhibits cell growth. c Clonogenic assay, PA28α silencing in CAL27 and HSC3 inhibits clonogenic. d Edu assay, PA28α silencing in CAL27 and HSC3 inhibits proliferation. e TUNEL assay, PA28α silencing in CAL27 and HSC3 has no effect on apoptosis. PA28α overexpression in OSCC cell lines promotes cell proliferation in vitro was indicated in Additional file 8: Figure S5. Data are reported as means ± SEM for three independantly experiments. (ANOVA or T test, *p < 0.05, ** p < 0.01, *** p < 0.001)
Mentions: Three PA28α targeting siRNAs were designed to downregulate PA28α expression. Two PA28α overexpressing OSCC cell lines, CAL27 and HSC3, were transfected with the most effective siRNA-PA28α while PA28 β and γ weren't affected (Additional file 7: Figure S4), following with tests of cells and subjected to MTT, colony formation, Edu coporation assay and TUNEL assay. PA28 knockdown (Fig. 3a) in CAL27 and HSC3 decreased cells viability, colony formation and cells proliferation (Fig. 3b, c, d), but no effects on apoptosis of these cells (Fig. 3e).Fig. 3

Bottom Line: PA28α was found to be overexpressed in OSCC cell lines and tumor tissues.Specific knockdown of PA28α inhibited OSCC cell proliferation, migration, invasion in vitro and reduced the growth of OSCC xenografts in vivo.These results suggest that PA28α is involved in OSCC oncogenesis and may serve as a potential prognostic factor.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, No. 14, Sec.3, Renminnan Road, Chengdu, Sichuan, 610041, China. fengxiaodong84@126.com.

ABSTRACT

Background: Despite recent advances in oral squamous cell carcinoma (OSCC) diagnosis and therapy, disease recurrence remains common and is strongly associated with mortality. It is therefore critical to identify new targets for both treatment and diagnostic purposes. We aimed at investigating the role of PA28α, a proteasomal activator in OSCC.

Methods: The expression of PA28α was examined in a panel of OSCC cell lines and tissues, associated with oncomine analysis. In a large OSCC patient cohort, the prognostic value of PA28α expression was evaluated. Primary clinical end points were recurrence-free and overall survival rate. Functional involvement of PA28α in OSCC was examined in both in vitro and in vivo models upon specific siRNA knockdown.

Results: PA28α was found to be overexpressed in OSCC cell lines and tumor tissues. High expression of PA28α was significantly associated with recurrence and poorer overall survival. Specific knockdown of PA28α inhibited OSCC cell proliferation, migration, invasion in vitro and reduced the growth of OSCC xenografts in vivo. Multivariate Cox regression analyses revealed PA28α as independent prognostic predictors.

Conclusions: These results suggest that PA28α is involved in OSCC oncogenesis and may serve as a potential prognostic factor.

No MeSH data available.


Related in: MedlinePlus