[Effect of Hematopoietic Pre-B-cell Leukemia Transcription Factor Interacting Protein Knockdown on Proliferation,Cell Cycle and Apoptosis in Pancreatic Cancer Cells].

Objective To unravel the role of hematopoietic pre-B-cell leukemia transcription factor interacting protein(HPIP)in the proliferation,cell cycle,and apoptosis of pancreatic ductal adenocarcinoma(PDAC)cells. Methods The HPIP expression in PDAC tissue was determined by immunohistochemical staining.Knockdown of HPIP was accomplished in MIA PaCa-2 and BxPC-3 cell lines by transient transfection of HPIP siRNA and validated by Western blotting.Cell proliferation was assessed using the cell counting kit-8 assay and colony formation assay.Cell cycle and apoptosis were detected by flow cytometry.Western blotting was performed to detect the expression levels of cyclin D1,caspase 7,and cleaved caspase 7. Results HPIP was overexpressed in PDAC tissue compared with matched adjacent pancreatic tissue(Z=-2.060,P=0.039).Knockdown of HPIP inhibited the proliferation of MIA PaCa-2 and BxPC-3 cells(all P<0.05).Knockdown of HPIP significantly reduced the positive colonies formed by MIA PaCa-2 and BxPC-3 cells(t=4.706,P=0.009;t=9.514,P=0.000).Knockdown of HPIP decreased the proportion of S phase cells(t=7.642,P=0.001;t=2.714,P=0.051)and increased the proportion of G0/G1 phase cells(t=3.244,P=0.031;t=6.095,P=0.003)in MIA PaCa-2 and BxPC-3 cells.Meanwhile,knockdown of HPIP increased the proportions of late-phase MIA PaCa-2 and BxPC-3 cells(t=24.58,P=0.000;t=36.45,P=0.000)and the overall apoptosis rate(t=29.43,P=0.000;t=43.52,P=0.000).In MIA PaCa-2 and BxPC-3 cells,knockdown of HPIP decreased the expression level of cyclin D1(t=6.705,P=0.002;t=6.238,P=0.003)and increased the expression level of cleaved caspase 7(t=3.991,P=0.016;t=6.536,P=0.002). Conclusions HPIP is overexpressed in PDAC tissue.Knockdown of HPIP inhibits the proliferation and G0/G1 to S transition of PDAC cells.Meanwhile,knockdown of HPIP promotes the apoptosis of PDAC cells.Thus,HPIP may act as an oncogene in PDAC.

Effect of Hematopoietic Pre-B-cell Leukemia Transcription Factor Interacting Protein Knockdown on Proliferation,Cell Cycle and Apoptosis in Pancreatic Cancer Cells / 中国医学科学院学报

To unravel the role of hematopoietic pre-B-cell leukemia transcription factor interacting protein(HPIP)in the proliferation,cell cycle,and apoptosis of pancreatic ductal adenocarcinoma(PDAC)cells. The HPIP expression in PDAC tissue was determined by immunohistochemical staining.Knockdown of HPIP was accomplished in MIA PaCa-2 and BxPC-3 cell lines by transient transfection of HPIP siRNA and validated by Western blotting.Cell proliferation was assessed using the cell counting kit-8 assay and colony formation assay.Cell cycle and apoptosis were detected by flow cytometry.Western blotting was performed to detect the expression levels of cyclin D1,caspase 7,and cleaved caspase 7. HPIP was overexpressed in PDAC tissue compared with matched adjacent pancreatic tissue(=-2.060,=0.039).Knockdown of HPIP inhibited the proliferation of MIA PaCa-2 and BxPC-3 cells(all <0.05).Knockdown of HPIP significantly reduced the positive colonies formed by MIA PaCa-2 and BxPC-3 cells(=4.706,=0.009;=9.514,=0.000).Knockdown of HPIP decreased the proportion of S phase cells(=7.642,=0.001;=2.714,=0.051)and increased the proportion of G/G phase cells(=3.244,=0.031;=6.095,=0.003)in MIA PaCa-2 and BxPC-3 cells.Meanwhile,knockdown of HPIP increased the proportions of late-phase MIA PaCa-2 and BxPC-3 cells(=24.58,=0.000;=36.45,=0.000)and the overall apoptosis rate(=29.43,=0.000;=43.52,=0.000).In MIA PaCa-2 and BxPC-3 cells,knockdown of HPIP decreased the expression level of cyclin D1(=6.705,=0.002;=6.238,=0.003)and increased the expression level of cleaved caspase 7(=3.991,=0.016;=6.536,=0.002). HPIP is overexpressed in PDAC tissue.Knockdown of HPIP inhibits the proliferation and G/G to S transition of PDAC cells.Meanwhile,knockdown of HPIP promotes the apoptosis of PDAC cells.Thus,HPIP may act as an oncogene in PDAC.

Expression and clinicopathological significance of hematopoietic pre-B cell leukemia transcription factor-interacting protein in cervical carcinoma.

Hematopoietic pre-B-cell leukemia transcription factor(PBX)-interacting protein (HPIP) is overexpressed in various malignancies, but its role in cervical cancer (CC) remains unknown. This study investigated the correlations of HPIP expression with clinicopathological factors and prognosis of cervical carcinoma patients. Expression of HPIP was detected in CC from 167 patients along with 45 corresponding normal cervical specimens by immunohistochemistry. HPIP immunoreactivity was overexpressed in CC cases compared with that in normal endometrium (P < 0.05). High HPIP expression was positively correlated with FIGO stage, histological grade, lymph node metastasis and recurrence (P < 0.05). Patients with high HPIP expression exhibited significantly poorer overall survival (OS) and disease-free survival (DFS) than patients with low HPIP expression (both P < 0.001). Cox multivariate analysis showed that high HPIP expression was an independent prognostic factor for both OS [hazard ratio (HR) = 8.791, 95% confidence interval (CI) = 2.098-36.826; P = 0.003 and DFS of patients with CC (HR = 10.485, 95% CI = 2.512-36.826; P = 0.001)]. We identified HPIP protein expression as a novel independent poor prognostic indicator in CC.

The clinical significance of HPIP and the associated prognosis in cervical cancer.

Hematopoietic pre-B-cell leukemia transcription factor-interacting protein (HPIP), is known to promote tumor development and metastasis. However its role in cervical cancer remains unknown. The purpose of this study was to investigate the clinical significance of HPIP expression and the prognosis of patients with cervical cancer. Fresh frozen tissues from 10 samples of cervical cancer and 8normal cervical tissues were analyzed for HPIP expression using real-time reverse transcription PCR and Western blot analysis. A total of 129 paraffin-embedded surgical specimens from patients with CC were collected for an immunohistochemistry assay to measure HPIP expression. Correlations of HPIP expression with clinicopathological factors and prognosis of patients with cervical cancer were analyzed. The HPIP expression at both the mRNA and protein levels was significantly higher in cervical cancer tissues than in normal cervical tissues (P<0.001). HPIP overexpression was significantly associated with high FIGO stage (P=0.005), Histological grade (P<0.001), Ascular tumor embolus (P=0.004), Iinterstitial infiltration (P<0.001), Tumor size (P=0.001) and Lymph node metastasis (P=0.005). Moreover, results revealed that HPIP expression was an independently prognostic factor for both overall survival [hazard ratio (HR): 8.874; 95% CI: 1.186-66.393; P=0.033] and disease-free survival [(HR): 11.523; 95% CI: 1.531-86.746; P=0.018] in patients with cervical cancer. The present study provides evidence that HPIP predicts metastasis and poor survival, highlighting its potential function as a therapeutic target for cervical cancer.

Expression of HPIP in epithelial ovarian carcinoma: a clinicopathological study.

OBJECTIVES: Hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP) plays an important role in cancer invasion and metastasis. The aim of this study is to investigate the expression of HPIP in epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Immunohistochemical method was performed using 42 normal ovarian specimens and 145 specimens with EOC. The correlations of HPIP expression with the clinicopathological factors and prognosis of EOC patients were evaluated. Statistical analyses were performed using the chi-square test, multivariate Cox proportional hazard, and Kaplan-Meier method. RESULTS: HPIP expression in EOC was higher than that in normal tissues (P<0.001). HPIP expression was significantly associated with histological grade, International Federation of Gynecology and Obstetrics stage, and lymphatic metastasis of EOC (P<0.05). Patients with high HPIP expression had poorer overall survival and disease-free survival (P<0.001) compared with patients with low HPIP expression. Multivariate Cox analysis demonstrated that HPIP was an independent factor for overall survival and disease-free survival (P<0.05). CONCLUSION: HPIP may be a valuable biomarker for predicting the prognosis of EOC patients and may serve as a potential target for cancer therapy.

Potential role of hematopoietic pre-B-cell leukemia transcription factor-interacting protein in oral carcinogenesis.

BACKGROUND: Hematopoietic pre-B-cell leukemia transcription factor-interacting protein (HPIP) is a corepressor of pre-B-cell leukemia homeobox (PBX) 1 and is known to play a role in hematopoiesis. Recently, HPIP was demonstrated to promote breast cancer cell proliferation and hepatocellular carcinoma growth. Moreover, it has been revealed that homeobox and PBX proteins, the expression of which is regulated by HPIP, play key roles in cancer of various organs, including oral squamous cell carcinoma (OSCC). Nevertheless, there has not been any study regarding the role of HPIP in OSCC. This study investigated the expression of HPIP in normal oral mucosa, epithelial precursor lesion (OEPL), and OSCC, and the functional roles of HPIP in OSCC cells and normal keratinocytes. MATERIALS AND METHODS: Immunohistochemical analysis of HPIP, Ki-67, and involucrin was performed in OSCC specimens, and the change in involucrin expression following RNA interference treatment against HPIP was examined by quantitative RT-PCR and Western blot analysis in SCC9 and NHEK cells undergoing extracellular calcium-induced differentiation. Matrigel transwell and cell proliferation assays for both cell lines transfected with HPIP siRNA were also conducted. RESULTS: HPIP expression increased in OEPL and OSCC specimens. In vitro analysis revealed that HPIP suppressed differentiation and proliferation of SCC9 cells and transwell migration of NHEK cells, while HPIP promoted invasion of SCC9 and proliferation of NHEK cells. However, HPIP has no significant effect on NHEK cell differentiation. CONCLUSION: HPIP may play a critical role in oral carcinogenesis and is thus a potential target for anticancer therapy, with particular emphasis on its involvement in differentiation and migration/metastasis.