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Increased RIPK4 expression is associated with progression and poor prognosis in cervical squamous cell carcinoma patients.

Liu DQ, Li FF, Zhang JB, Zhou TJ, Xue WQ, Zheng XH, Chen YB, Liao XY, Zhang L, Zhang SD, Hu YZ, Jia WH - Sci Rep (2015)

Bottom Line: Further, RIPK4 overexpression was associated with overall (HR = 2.085, P = 0.038) and disease-free survival (HR = 1.742, P = 0.037).Knockdown of RIPK4 reduced cell migration and invasion via inhibition of Vimentin, MMP2 and Fibronectin expression in cervical cancer cells.RIPK4 might act as a potential diagnostic and independent prognostic biomarker for CSCC patients.

View Article: PubMed Central - PubMed

Affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

ABSTRACT
Aberrant expression of receptor interacting protein kinase 4 (RIPK4), a crucial regulatory protein of Wnt/β-catenin signaling, has recently been reported to be involved in several cancers. Here, we report the potential clinical implication and biological functions of RIPK4 in cervical squamous cell carcinoma (CSCC). One hundred and ninety-eight CSCC cases, 109 low-grade squamous intraepithelial lesions (LSILs), 141 high-grade squamous intraepithelial lesions (HSILs) and 63 chronic cervicitis were collected. The expression of RIPK4 was detected by immunohistochemistry (IHC), and its clinical value and oncogenic functions were further assessed. RIPK4 expression increased significantly with disease progression from 3.2% in chronic cervicitis, 19.3% in LSILs and 85.1% in HSILs to 94.4% in CSCCs (P < 0.001). Moreover, RIPK4 may serve as a useful biomarker to distinguish HSIL from chronic cervicitis/LSIL, which are two different clinical types for therapeutic procedures, with a high sensitivity and specificity (85.1% and 86.6%, respectively) and the performance improved when combined with p16(INK4a). Further, RIPK4 overexpression was associated with overall (HR = 2.085, P = 0.038) and disease-free survival (HR = 1.742, P = 0.037). Knockdown of RIPK4 reduced cell migration and invasion via inhibition of Vimentin, MMP2 and Fibronectin expression in cervical cancer cells. RIPK4 might act as a potential diagnostic and independent prognostic biomarker for CSCC patients.

No MeSH data available.


Related in: MedlinePlus

RIPK4 depletion decreases cell proliferation and colony formation capability in SiHa and Caski cells in vitro.(a, b) Real-time quantitative PCR analysis of RIPK4 mRNA expression and western blot analysis of RIPK4 protein expression in SiHa and Caski cells transfected with specific siRNAs targeting RIPK4 for 48 h. (c, d) Colony formation capacity of SiHa and Caski cells transfected with RIPK4 siRNAs and control siRNA were analyzed by colony formation assay. (e) Inhibition of SiHa cell proliferation by RIPK4 siRNAs tested by MTT assays. (f) Inhibition of Caski cell proliferation by RIPK4 siRNAs as measured by MTT assays. Values are the mean ± s.d. of three independent experiments. *P < 0.05 relative to the control.
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f3: RIPK4 depletion decreases cell proliferation and colony formation capability in SiHa and Caski cells in vitro.(a, b) Real-time quantitative PCR analysis of RIPK4 mRNA expression and western blot analysis of RIPK4 protein expression in SiHa and Caski cells transfected with specific siRNAs targeting RIPK4 for 48 h. (c, d) Colony formation capacity of SiHa and Caski cells transfected with RIPK4 siRNAs and control siRNA were analyzed by colony formation assay. (e) Inhibition of SiHa cell proliferation by RIPK4 siRNAs tested by MTT assays. (f) Inhibition of Caski cell proliferation by RIPK4 siRNAs as measured by MTT assays. Values are the mean ± s.d. of three independent experiments. *P < 0.05 relative to the control.

Mentions: To further investigate the functional role of RIPK4 in cervical cancer cells, we silenced its expression using two specific small interference RNAs (siRNAs) in SiHa and Caski cells. As shown in Fig. 3a,b, RIPK4 mRNA and protein levels were efficiently downregulated in cells transfected with specific siRNAs for RIPK4 compared with those transfected with control siRNA. We then assessed the impact of RIPK4 ablation on cell proliferation and clone formation in vitro. The cell proliferation and clone formation capacity were markedly inhibited after knockdown of RIPK4 expression in SiHa and Caski cells when compared with control siRNA treatment (P < 0.01; Fig. 3c,d,e,f). Collectively, these data suggested that RIPK4 played an important role in the growth of cervical cancer cells. In the migration assay, the cell migration rates were significantly suppressed after knockdown of RIPK4 expression in SiHa and Caski cells when compared with control siRNA treatment (P < 0.01; Fig. 4a). In addition, the Matrigel invasion assay demonstrated that knockdown of RIPK4 expression significantly suppressed the invasiveness of SiHa and Caski cells (P < 0.01; Fig. 4b).


Increased RIPK4 expression is associated with progression and poor prognosis in cervical squamous cell carcinoma patients.

Liu DQ, Li FF, Zhang JB, Zhou TJ, Xue WQ, Zheng XH, Chen YB, Liao XY, Zhang L, Zhang SD, Hu YZ, Jia WH - Sci Rep (2015)

RIPK4 depletion decreases cell proliferation and colony formation capability in SiHa and Caski cells in vitro.(a, b) Real-time quantitative PCR analysis of RIPK4 mRNA expression and western blot analysis of RIPK4 protein expression in SiHa and Caski cells transfected with specific siRNAs targeting RIPK4 for 48 h. (c, d) Colony formation capacity of SiHa and Caski cells transfected with RIPK4 siRNAs and control siRNA were analyzed by colony formation assay. (e) Inhibition of SiHa cell proliferation by RIPK4 siRNAs tested by MTT assays. (f) Inhibition of Caski cell proliferation by RIPK4 siRNAs as measured by MTT assays. Values are the mean ± s.d. of three independent experiments. *P < 0.05 relative to the control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493702&req=5

f3: RIPK4 depletion decreases cell proliferation and colony formation capability in SiHa and Caski cells in vitro.(a, b) Real-time quantitative PCR analysis of RIPK4 mRNA expression and western blot analysis of RIPK4 protein expression in SiHa and Caski cells transfected with specific siRNAs targeting RIPK4 for 48 h. (c, d) Colony formation capacity of SiHa and Caski cells transfected with RIPK4 siRNAs and control siRNA were analyzed by colony formation assay. (e) Inhibition of SiHa cell proliferation by RIPK4 siRNAs tested by MTT assays. (f) Inhibition of Caski cell proliferation by RIPK4 siRNAs as measured by MTT assays. Values are the mean ± s.d. of three independent experiments. *P < 0.05 relative to the control.
Mentions: To further investigate the functional role of RIPK4 in cervical cancer cells, we silenced its expression using two specific small interference RNAs (siRNAs) in SiHa and Caski cells. As shown in Fig. 3a,b, RIPK4 mRNA and protein levels were efficiently downregulated in cells transfected with specific siRNAs for RIPK4 compared with those transfected with control siRNA. We then assessed the impact of RIPK4 ablation on cell proliferation and clone formation in vitro. The cell proliferation and clone formation capacity were markedly inhibited after knockdown of RIPK4 expression in SiHa and Caski cells when compared with control siRNA treatment (P < 0.01; Fig. 3c,d,e,f). Collectively, these data suggested that RIPK4 played an important role in the growth of cervical cancer cells. In the migration assay, the cell migration rates were significantly suppressed after knockdown of RIPK4 expression in SiHa and Caski cells when compared with control siRNA treatment (P < 0.01; Fig. 4a). In addition, the Matrigel invasion assay demonstrated that knockdown of RIPK4 expression significantly suppressed the invasiveness of SiHa and Caski cells (P < 0.01; Fig. 4b).

Bottom Line: Further, RIPK4 overexpression was associated with overall (HR = 2.085, P = 0.038) and disease-free survival (HR = 1.742, P = 0.037).Knockdown of RIPK4 reduced cell migration and invasion via inhibition of Vimentin, MMP2 and Fibronectin expression in cervical cancer cells.RIPK4 might act as a potential diagnostic and independent prognostic biomarker for CSCC patients.

View Article: PubMed Central - PubMed

Affiliation: Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

ABSTRACT
Aberrant expression of receptor interacting protein kinase 4 (RIPK4), a crucial regulatory protein of Wnt/β-catenin signaling, has recently been reported to be involved in several cancers. Here, we report the potential clinical implication and biological functions of RIPK4 in cervical squamous cell carcinoma (CSCC). One hundred and ninety-eight CSCC cases, 109 low-grade squamous intraepithelial lesions (LSILs), 141 high-grade squamous intraepithelial lesions (HSILs) and 63 chronic cervicitis were collected. The expression of RIPK4 was detected by immunohistochemistry (IHC), and its clinical value and oncogenic functions were further assessed. RIPK4 expression increased significantly with disease progression from 3.2% in chronic cervicitis, 19.3% in LSILs and 85.1% in HSILs to 94.4% in CSCCs (P < 0.001). Moreover, RIPK4 may serve as a useful biomarker to distinguish HSIL from chronic cervicitis/LSIL, which are two different clinical types for therapeutic procedures, with a high sensitivity and specificity (85.1% and 86.6%, respectively) and the performance improved when combined with p16(INK4a). Further, RIPK4 overexpression was associated with overall (HR = 2.085, P = 0.038) and disease-free survival (HR = 1.742, P = 0.037). Knockdown of RIPK4 reduced cell migration and invasion via inhibition of Vimentin, MMP2 and Fibronectin expression in cervical cancer cells. RIPK4 might act as a potential diagnostic and independent prognostic biomarker for CSCC patients.

No MeSH data available.


Related in: MedlinePlus