Circ_0070203 Promotes Epithelial-mesenchymal Transition in Ovarian Serous Cystadenocarcinoma through miR-370-3p/TGFßR2 Axis.

INTRODUCTION: Circular RNAs (circRNAs) are important biological molecules associated with the pathogenesis of multiple cancers. OBJECTIVE: This work aimed to investigate the function and molecular mechanism of circ_0070203 in high-grade serous ovarian cystadenocarcinoma (HGSOC). METHODS: circRNA microarray was conducted to detect the circ_0070203 expression in HGSOC tissues. Bioinformatics analysis was used to find the binding sites between circ_0070203, miR- 370-3p and TGFßR2. Real-time quantitative reverse transcription PCR (RT-qPCR) was executed to detect the expressions of circ_0070203, miR-370-3p and TGFßR2 in HGSOC tissues and SKOV3 cells. Dual-luciferase reporter gene assay was used to validate the relationships between miR-370-3p and circ_0070203 or TGFßR2. Besides, transwell assays were conducted to assess the migrative, invasive abilities of ovarian cancer (OC) cells. Western blotting was adopted to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins. The related patents were also studied during the research. RESULTS: Circ_0070203 and TGFßR2 were upregulated, while miR-370-3p was downregulated in FIGO stage III-IV HGSOC tissues and SKOV-3 cell lines. circ_0070203 overexpression changed the expression of other EMT-related proteins and enhanced the migrative, invasive abilities of OC cells, while silencing circ_0070203 worked oppositely. Mechanistically, circ_0070203 could upregulate TGFßR2 expression in OC cells via sponging miR-370-3p. CONCLUSION: Circ_0070203 could promote the epithelial-mesenchymal transition, invasion, and metastasis of HGSOC via regulating the miR-370-3p/TGFßR2 axis. Our findings provided a potential biomarker for HGSOC therapy.

Targeting MYH9 represses USP14-mediated NAP1L1 deubiquitination and cell proliferation in glioma.

Myosin heavy chain 9 (MYH9) plays an important role in a number of diseases. Nevertheless, the function of MYH9 in glioma is unclear. The present research aimed to investigate the role of MYH9 in glioma and determine whether MYH9 is involved in the temozolomide chemoresistance of glioma cells. Our results showed that MYH9 increased the proliferation and temozolomide resistance of glioma cells. The mechanistic experiments showed that the binding of MYH9 to NAP1L1, a potential promoter of tumor proliferation, inhibited the ubiquitination and degradation of NAP1L1 by recruiting USP14. Upregulation of NAP1L1 increased its binding with c-Myc and activated c-Myc, which induced the expression of CCND1/CDK4, promoting glioma cell temozolomide resistance and proliferation. Additionally, we found that MYH9 upregulation was strongly related to patient survival and is therefore a negative factor for patients with glioma. Altogether, our results show that MYH9 plays a role in glioma progression by regulating NAP1L1 deubiquitination. Thus, targeting MYH9 is a potential therapeutic strategy for the clinical treatment of glioma in the future.

MYH10 Combines with MYH9 to Recruit USP45 by Deubiquitinating Snail and Promotes Serous Ovarian Cancer Carcinogenesis, Progression, and Cisplatin Resistance.

The poor prognosis of serous ovarian cancer (SOC) is due to its high invasive capacity and cisplatin resistance of SOC cells, whereas the molecular mechanisms remain poorly understood. In the present study, the expression and function of non-muscle myosin heavy chain IIB (MYH10) in SOC are identified by immunohistochemistry, in vitro, and in vivo studies, respectively. The mechanism of MYH10 is demonstrated by co-immunoprecipitation, GST pull-down, confocal laser assays, and so on. The results show that the knockdown of MYH10 suppressed SOC cell proliferation, migration, invasion, metastasis, and cisplatin resistance both in vivo and in vitro. Further studies confirm that the MYH10 protein functional domain combines with non-muscle myosin heavy chain IIA (MYH9) to recruit the deubiquitinating enzyme Ubiquitin-specific proteases 45 and deubiquitinates snail to inhibit snail degradation, eventually promoting tumorigenesis, progression, and cisplatin resistance in SOC. In clinical samples, MYH10 expression is significantly elevated in SOC samples compared to the paratumor samples. And the expression of MYH10 is positively correlated with MYH9 expression. MYH10+/MYH9+ co-expression is an independent prognostic factor for predicting SOC patient survival. These findings uncover a key role of the MYH10-MYH9-snail axis in SOC carcinogenesis, progression, and cisplatin resistance, and provide potential novel therapeutic targets for SOC intervention.

NAP1L1 promotes proliferation and chemoresistance in glioma by inducing CCND1/CDK4/CDK6 expression through its interaction with HDGF and activation of c-Jun.

The prognosis of glioma is poor as its pathogenesis and mechanisms underlying cisplatin chemoresistance remain unclear. Nucleosome assembly protein 1 like 1 (NAP1L1) is regarded as a hallmark of malignant tumors. However, the role of NAP1L1 in glioma remains unknown. In this study, we aimed to investigate the molecular functions of NAP1L1 in glioma and its involvement in cisplatin chemoresistance, if any. NAP1L1 was found to be upregulated in samples from The Cancer Genome Atlas (TCGA) database. Immunohistochemistry indicated that NAP1L1 and hepatoma-derived growth factor (HDGF) were enhanced in glioma as compared to the para-tumor tissues. High expressions of NAP1L1 and HDGF were positively correlated with the WHO grade, KPS, Ki-67 index, and recurrence. Moreover, NAP1L1 expression was also positively correlated with the HDGF expression in glioma tissues. Functional studies suggested that knocking down NAP1L1 could significantly inhibit glioma cell proliferation both in vitro and in vivo, as well as enhance the sensitivity of glioma cells to cisplatin (cDDP) in vitro. Mechanistically, NAP1L1 could interact with HDGF at the protein level and they co-localize in the cytoplasm. HDGF knockdown in NAP1L1-overexpressing glioma cells significantly inhibited cell proliferation. Furthermore, HDGF could interact with c-Jun, an oncogenic transcription factor, which eventually induced the expressions of cell cycle promoters, CCND1/CDK4/CDK6. This finding suggested that NAP1L1 could interact with HDGF, and the latter recruited c-Jun, a key oncogenic transcription factor, that further induced CCND1/CDK4/CDK6 expression, thereby promoting proliferation and chemoresistance in glioma cells. High expression of NAP1L1 in glioma tissues indicated shorter overall survival in glioma patients.

High Expression of MYL9 Indicates Poor Clinical Prognosis of Epithelial Ovarian Cancer.

BACKGROUND: The prognosis of Epithelial Ovarian Cancer (EOC) is poor, but the prognostic biomarkers are neither sensitive nor specific. Therefore, it is very important to search novel prognostic biomarkers for EOC. OBJECTIVES: The present study aimed to investigate Myosin Light Chain 9(MYL9) expression in Epithelial Ovarian Cancer (EOC) tissues (including paraffin-embedded and fresh tissue samples) and its relationship with clinicopathological characteristics, as well as its potential prognostic value in patients with EOC. METHODS: Between March 2009 and December 2018, all of 184 paraffin-embedded cancer tissues from patients with EOC and 41 paratumor tissues, pathologically confirmed at the Memorial Hospital of Sun Yat-sen University and Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, were collected for the present study and were assessed for MYL9 protein expression patterns using Immunohistochemistry (IHC). Furthermore, from August 2013 to November 2019, 16 fresh EOC tissues and their paired paratumor tissues, pathologically confirmed at the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University were analyzed using Reverse-Transcription Quantitative PCR (RT-qPCR) to detect MYL9 mRNA expression levels. RESULTS: The results showed that MYL9 expression was higher in cancer tissues compared with that in paratumor tissues, and MYL9 overexpression was associated with shorter Recurrence Free Survival (RFS) and Overall Survival (OS) of EOC patients. Furthermore, multivariate Cox model analysis indicated that MYL9 overexpression was an independent poor survival prediction in patients with EOC. CONCLUSION: MYL9 is upregulated in EOC and may serve as a useful patent of prognostic biomarker in EOC, and it may demonstrate an important value for the clinical treatment and supervision of patients with EOC.

VPS33B interacts with NESG1 to suppress cell growth and cisplatin chemoresistance in ovarian cancer.

The pathogenesis and cisplatin chemoresistance of ovarian cancer (OC) are still unclear. Vacuolar protein sorting-associated 33B (VPS33B) has not been reported in OC to date. In this study, immunohistochemistry was used to detect VPS33B protein expression between OC and ovarian tissues. MTT, EdU, colony formation, cell cycle, in vivo tumorigenesis, western blot, ChIP, EMSA, co-immunoprecipitation (CoIP), qRT-PCR, and microconfocal microscopy were used to explore the function and molecular mechanisms of VPS33B in OC cells. The results of the present study demonstrated that VPS33B protein expression was obviously reduced in OC compared with that in ovarian tissues. Overexpressed VPS33B suppressed cell cycle transition, cell growth, and chemoresistance to cisplatin in vitro and in vivo. Analysis of the mechanism indicated that overexpressed VPS33B regulated the epidermal growth factor receptor (EGFR)/PI3K/AKT/c-Myc/p53/miR-133a-3p feedback loop and reduced the expression of the cell cycle factor CDK4. Nasopharyngeal epithelium-specific protein 1 (NESG1) as a tumor suppressor not only interacted with VPS33B, but was also induced by VPS33B by the attenuation of PI3K/AKT/c-Jun-mediated transcription inhibition. Overexpressed NESG1 further suppressed cell growth by mediating VPS33B-modulated signals in VPS33B-overexpressing OC cells. Finally, NESG1 induced VPS33B expression by reducing the inhibition of PI3K/AKT/c-Jun-mediated transcription. Our study is the first to demonstrate that VPS33B serves as a tumor suppressor, and VPS33B can interact with NESG1 to suppress cell growth and promote cisplatin sensitivity by regulating the EGFR/PI3K/AKT/c-Myc/p53/miR-133a-3p feedback loop in OC cells.

Expression and Clinical Significance of Microtubule-Actin Cross-Linking Factor 1 in Serous Ovarian Cancer.

BACKGROUND: Ovarian Cancer (OC) remains the first leading cause of gynecologic malignancy. The survival rate from Serous Ovarian Cancer (SOC) is very low, and the present prognostic predictors of SOC are not very sensitive or specific. OBJECTIVE: The present study aimed to investigate Microtubule-Actin Cross-Linking Factor 1 (MACF1) expression in SOC tissues (including paraffin-embedded and fresh tissues) and to assess its expression and significant value in patients with SOC. METHODS: A total of 18 fresh SOC tissues and their paired paratumor tissues were performed with reverse-transcription quantitative PCR analysis to detect MACF1 mRNA expression. Moreover, 175 paraffin-embedded SOC tissues and 41 paratumor tissues were assessed for MACF1 expression using immunohistochemistry. RESULTS: The mRNA and protein expression of MACF1, both were higher in cancer tissues than that in paratumor tissues, and the high expression of MACF1 was associated with shorter Recurrence Free Survival (RFS) and Overall Survival (OS) in patients with SOC. Furthermore, multivariate regression analysis showed that high MACF1 expression was an independent poor survival predictor of patients with SOC. CONCLUSION: MACF1 is upregulated in SOC, and it may be used as a useful prognostic biomarker in SOC.

Co-Overexpression of GRK5/ACTC1 Correlates With the Clinical Parameters and Poor Prognosis of Epithelial Ovarian Cancer.

Background: The prognosis of epithelial ovarian cancer (EOC) is poor, and the present prognostic predictors of EOC are neither sensitive nor specific. Objective: The aim of this study was to search the prognostic biomarkers of EOC and to investigate the expression of G protein-coupled receptor kinase 5 (GRK5) and actin alpha cardiac muscle 1 (ACTC1) in EOC tissues (both paraffin-embedded and fresh-frozen tissues) and to explore their association with clinicopathological parameters and prognostic value in patients with EOC. Methods: A total of 172 paraffin-embedded cancer tissues of EOC patients diagnosed and operated at the memorial hospital of Sun Yat-sen University between December 2009 and March 2017 and 41 paratumor tissues were collected and the expression of GRK5 and ACTC1 was examined using immunohistochemistry. Furthermore, 16 fresh-frozen EOC tissues and their matched paratumor tissues were collected from the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, between August 2013 and November 2019 and subjected to reverse-transcription quantitative PCR analysis to detect the mRNA expression of GRK5 and ACTC1. Results: The expression of GRK5 and ACTC1 was both higher in cancer tissues than in paratumor tissues. GRK5 expression was positively correlated with ACTC1 expression. In addition, GRK5, ACTC1, and GRK5/ACTC1 expression was associated with the recurrence-free survival and overall survival of EOC patients. Furthermore, multivariate logistic regression analysis indicated that GRK5+/ACTC1+ co-expression, intestinal metastasis, postoperative chemotherapy, platinum resistance, and hyperthermic intraperitoneal chemotherapy were independent prognostic factors of EOC. Conclusion: GRK5 and ACTC1 are both upregulated in EOC compared with those in paratumor tissues. The co-expression of GRK5+/ACTC1+ rather than GRK5 or ACTC1 is an independent prognostic biomarker of EOC.

FOXO1 overexpression is correlated with poor prognosis in epithelial ovarian cancer.

OBJECTIVE: To investigate FOXO1 expression in epithelial ovarian cancer (EOC), and to explore its correlation with clinicopathological parameters and prognosis of EOC. METHODS: Two hundred and sixteen cases of paraffin-embedded EOC and 41 paratumor tissues from 2009 to 2017 that had been pathologically confirmed at the memorial hospital of Sun Yat-sen University were included in this study, and the expression of FOXO1 was performed by immunohistochemistry using a polyclonal antibody specific for FOXO1. RESULTS: FOXO1 protein expression is associated with Recurrence free and overall survival in EOC patients; In addition, FOXO1 expression is associated with age, FIGO stage, intraperitoneal metastasis, intestinal metastasis, vital status, intraperitoneal recurrence and differentiation grade; Moreover, in a multivariate model FOXO1 overexpression was an independent predictor of poor survival in EOC. CONCLUSION: FOXO1 may play a candidate oncogenic role in EOC, and FOXO1 is a useful independent prognostic marker in EOC, and it may provide a candidate target therapy in future.

LGR4 overexpression is associated with clinical parameters and poor prognosis of serous ovarian cancer.

OBJECTIVE: LGR4 expression in serous ovarian cancer paraffin-embedded tissues and fresh tissues were investigated, and its expression associated with clinicopathological parameters and prognosis in serous ovarian cancer was explored. METHODS: From Dec, 2009 to Jan, 2020, 122 paraffin-embedded serous ovarian cancer patients and 41 paired paratumor tissues who were both diagnosed and operated at the memorial hospital of Sun Yat-sen University and Integrated Hospital of Traditional Chinese Medicine, Southern Medical University were selected in this research, respectively, and all of these tissues were performed by immunohistochemistry (IHC) with a polyclonal antibody for LGR4. Meanwhile, from Aug, 2013 to Mar, 2019, 15 cases of serous ovarian cancer fresh tissues and 15 cases of paratumor fresh tissues who were operated at Integrated Hospital of Traditional Chinese Medicine, Southern Medical University were performed with Quantitative Real-time PCR to detect the mRNA expression of LGR4, respectively. RESULTS: LGR4 expression was much higher both in paraffin-embedded and fresh cancer tissues than that in paratumor tissues, respectively, and its expression was associated with recurrence free survival and overall survival in serous ovarian cancer patients. Moreover, in a multivariate model LGR4 was an indeed independent predictor of poor survival in serous ovarian cancer patients. CONCLUSION: LGR4 is upregulated in serous ovarian cancer, and LGR4 is an indeed useful independent prognostic predictor in serous ovarian cancer, and it may provide important clinical value of serous ovarian cancer.

miR-6089/MYH9/ß-catenin/c-Jun negative feedback loop inhibits ovarian cancer carcinogenesis and progression.

The pathogenesis of ovarian cancer remains to be elucidated. Our previous study demonstrated that myosin heavy chain 9 (MYH9) overexpression was associated with poor prognosis of epithelial ovarian cancer. However, the mechanism of MYH9 and its regulation by microRNA (miR) is not clear. The results of the present study demonstrated that miR-6089 was one of the microRNAs targeting MYH9, and miR-6089 overexpression suppressed ovarian cancer cell proliferation, migration, invasion and metastasis in vivo and in vitro. Mechanistic studies confirmed that miR-6089 directly targeted MYH9 to inactivate the Wnt/ß-catenin signalling pathway and its downstream epithelial-to-mesenchymal transition (EMT), cell-cycle factors and c-Jun, whereas overexpression of MYH9 reversed the inhibitory effects of miR-6089 overexpression in ovarian cancer cells by upregulating the Wnt/ß-catenin and its downstream EMT, cell-cycle factors and c-Jun. Interestingly, miR-6089 was transcriptionally inhibited by c-Jun, a transcription factor which could be induced by MYH9 via the Wnt/ß-catenin pathway. Thus miR-6089/MYH9/ß-catenin/c-Jun formed a negative feedback loop in ovarian cancer. In clinical samples, miR-6089 negatively correlated with MYH9 expression. Our study is the first to demonstrate that miR-6089 serves as a tumor-suppressive miRNA, and miR-6089/MYH9/ß-catenin/c-Jun negative feedback loop inhibits ovarian cancer carcinogenesis and progression.

Low expression of KIF7 indicates poor prognosis in epithelial ovarian cancer.

The aim of the present study was to investigate kinesin family member 7 (KIF7) expression in epithelial ovarian cancer tissues (paraffin-embedded tissues and fresh) and to explore its expression, association with clinicopathological parameters and prognostic value in patients with epithelial ovarian cancer. A total of 113 paraffin-embedded tumor tissues of epithelial ovarian cancer patients diagnosed and operated at the memorial hospital of Sun Yat-sen University Between December 2009 and March 2017 and 41 paratumor tissues were collected for the present study and were assessed for KIF7 expression using immunohistochemistry. Furthermore, 22 fresh epithelial ovarian cancer tissues and their matched paratumor tissues were collected from the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, between August 2013 and March 2019 and subjected to reverse-transcription quantitative PCR analysis to detect the mRNA expression of KIF7. The expression of KIF7 was lower in cancer tissues than in paratumor tissues, and KIF7 expression was associated with recurrence-free survival and overall survival in epithelial ovarian cancer patients. Furthermore, multivariate logistic regression analysis indicated that low KIF7 expression was an independent predictor of poor survival in patients with epithelial ovarian cancer. In conclusion, KIF7 has a tumor suppressor role in epithelial ovarian cancer and is a useful independent prognostic predictor. It may hold important value for the clinical diagnosis and treatment of epithelial ovarian cancer.

MYH9 overexpression correlates with clinicopathological parameters and poor prognosis of epithelial ovarian cancer.

The aim of the present study was to investigate the expression of myosin 9 (MYH9) in epithelial ovarian cancer and to explore its correlation with the clinicopathological parameters and prognosis of epithelial ovarian cancer (EOC). A total of 265 cases of paraffin-embedded ovarian cancer tissues and 41 paratumor tissues which had been pathologically confirmed at the Memorial Hospital of Sun Yat-sen University from 2009 to 2017 were included in the present study. MYH9 expression was investigated with immunohistochemistry using a polyclonal antibody specific for MYH9. MYH9 expression is associated with disease progression free and overall survival in epithelial ovarian cancer patients; and the expression of MYH9 is associated with International Federation of Gynecology and Obstetrics stage, lymph node metastasis, intraperitoneal metastasis, survival status (at last follow-up), intraperitoneal recurrence, residual tumor size and ascites with tumor cells. Moreover, in a multivariate model MYH9 overexpression was an independent predictor of poor survival in epithelial ovarian cancer. MYH9 may be a candidate that plays a oncogenic role in epithelial ovarian cancer. MYH9 is a useful independent prognostic marker in epithelial ovarian cancer, and it may provide a candidate target therapy treatment of ovarian cancer in the future.

Expression and clinical significance of transcription factor 4 (TCF4) in epithelial ovarian cancer.

OBJECTIVES: To investigate TCF4 expression in epithelial ovarian cancer, and to explore its correlation with clinicopathological parameters and clinical prognosis of epithelial ovarian cancer. METHODS: From 2009 to 2017, 188 cases of paraffin-embedded epithelial ovarian cancer tissues and 41 paratumor ovarian tissues which had been confirmed at the memorial hospital of Sun Yat-sen University were collected in this study, and the expression of TCF4 was performed by immunohistochemistry using a polyclonal antibody specific for TCF4. RESULTS: The expression of TCF4 protein was associated with disease progression free survival and overall survival in epithelial ovarian cancer patients; and TCF4 overexpression was associated with age, FIGO stage, lymph node metastasis, intraperitoneal metastasis, intestinal metastasis, vital status, intraperitoneal recurrence, and serum CA153. Moreover, in a multivariate Cox regression analysis TCF4 overexpression was an indeed independent prognostic factor in epithelial ovarian cancer. CONCLUSIONS: TCF4 may play an oncogenic role in epithelial ovarian cancer, and TCF4 is a useful independent prognostic biomarker of epithelial ovarian cancer, and it may provide a candidate target therapy treatment in future.

Preparation of boron nitride nanosheet-coated carbon fibres and their enhanced antioxidant and microwave-absorbing properties.

In this study, annealing carbon fibres with boron and FeCl3·6H2O at elevated temperatures was demonstrated as a novel route to coat carbon fibres with boron nitride (BN) nanosheets. The effect of annealing temperature on the thickness and microstructure of BN coating was investigated. Results showed that BN coating hardly formed at 1000 °C, and uniform BN coating was achieved at 1100 °C and 1200 °C. However, further increasing the temperature to 1250 °C triggered the formation of discretely distributed BN particles on the surface of the BN coating in addition to the formation of a uniform BN coating. The BN coating and particles were constructed by numerous BN nanosheets with a bending and crumpling morphology. The thickness of the BN coating increased with increasing annealing temperature. The oxidation resistance of the carbon fibres dramatically enhanced after BN nanosheets were coated onto the carbon fibre surface. Moreover, given the low dielectric loss tangent of BN, the BN coating can improve the impedance matching of carbon fibres and enhance the microwave-absorbing property of carbon fibres significantly.

Biological characteristics and construction of stable ALDH-1 knock-down Hela cell lines.

OBJECTIVES: To explore the relationship between aldehye dehydrogenase-1 (ALDH-1) and biological characteristics of the stable ALDH-1 knock-down Hela cell lines. MATERIALS AND METHODS: Transfected Hela cells with lentiviral vector were utilized and puromycin was used to screen and achieve the stable cell lines. The interference efficiency was calculated by performing qRT-PCR to detect the expression of ALDH-1 of three groups including the interfering group, the negative control (NC) group, and the normal Hela group. CCK-8 assays were used to detect the OD value of each group. The coloning formation rate of each group was detected by colony formation assay. cell cycle distribution and apoptosis of each group were also detected by employing cell cycle and apoptosis experiments. Results: The stable ALDH-1 knock-down Hela cell lines were successfully obtained after two weeks' screening; compared with the NC and Hela group, the ALDH-1 expression level of interfering group was 1.05 ± 0.10 (both p < 0.05), whose silencing efficiency was 80.59%. CCK-8 assays verified that the mean OD value of interfering group was lower than that of NC and Hela group. Additionally, colony formation assays showed that the coloning efficiency of interfering group was lower than that of NC and Hela group. Cell cycle experiments proved that the proportion of G0/G1 phase of interfering group was higher than that of the other two groups, while the proportion of S phase was lower. Cell apoptosis assays indicated that the apoptosis rate of interfering group was the highest. CONCLUSIONS: Constructing stable interfering Hela cell lines with lentiviral vectors was successful and worthy of promotion. ALDH-1 plays an important role in promoting cell growth and proliferation, maintaining cell cycle and inhibiting Hela cell apoptosis.

APOBEC3A possesses anticancer and antiviral effects by differential inhibition of HPV E6 and E7 expression on cervical cancer.

Cervical cancer is the second most common cancer among women worldwide and is the leading cause of deaths in developing countries. Persistent infections with a subset of HPVs, called "high-risk HPVs", including HPV16 and HPV18, are the primary cause of cervical cancer. The apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family of proteins is a group of cellular enzymes that catalyze the deamination of cytidine (C) to uracil (U) in single-stranded DNA/RNA, and functions as antiviral factors in the innate immune system of the host. Recent studies have shown that APOBEC3A could restrict certain DNA viruses, including HPVs. In this study, we confirmed that the expression of APOBEC3A was decreased in cervical cancer tissues. Furthermore, APOBEC3A inhibited the cervical cells proliferation, migration as well as invasion, and promoted apoptosis depend on cytidine deaminase. In addition, APOBEC3A decreased HPV16-E6, HPV16-E7 and HPV18-E6 depend on cytidine deaminase, but no effect on HPV18-E7. Therefore, we believe that, in cervical cancer cells, the expression of APOBEC3A possesses anticancer and antiviral effects by differential inhibition of HPV E6 and E7 expression depend on cytidine deaminase.

Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in cervical cancer.

BACKGROUND: Multiple studies proved that miRNAs have a causal role in tumorigenesis. Some miRNAs are regulated by epigenetic alterations in their promoter regions and can be activated by chromatin- modifying drugs. METHODS: We treated cervical cancer cells with 5-aza-2'-deoxycytidine and get a microarray analysis. Dysregulation of miRNAs was measured by qPCR in cervical cell lines and methylation status of them in cervical cancer tissue were performed with MeDIP-qPCR assay. RESULTS: We found hypermethylation of miR-432, miR-1286, miR-641, miR-1290, miR-1287 and miR-95 may have some relationship with HPV infection in cervical cell lines. In primary tumors of cervix with paired normal tissue, expression levels of miRNAs were inversely correlated with their DNA methylation status in the cervical cancer cell lines treated with 5-AZA. CONCLUSIONS: Our results indicate that miRNAs might play a role in the pathogenesis of human cervical cancer with HPV and identify altered miRNA methylation as a possible epigenetic mechanism involved in their aberrant expression.

[Clinical report of the modified Piver class III hysterectomy on invasive cervical cancer].

OBJECTIVE: To explore the surgical extent and to improve the surgical techniques of the Piver class III hysterectomy on invasive cervical cancer, so as to reduce the urinary tract complications, shorten the surgical duration, decrease the hemorrhage and blood transfusion. METHODS: The study group, 196 cases with stages Ib and IIa carcinoma of the cervix underwent the modified Piver class III hysterectomy from June 2000 to May 2005. The control group, 176 cases of the same stages underwent the Piver class III hysterectomy between June 1994 and May 1999. The modified Piver class III hysterectomy mainly include the surgical extent and some surgical techniques as follows. The cervicovesical and vesicovaginal space are separated with assistance of electrotome. Half of the uterosacral ligaments are removed with electrotome. The tunnel of the ureters is separated and penetrated or not. The anterior leaf of the cervicovesical ligaments is removed and the uterine artery are removed at the same time, while the ureter branch from the uterine artery are preserved. When the ureters are drawn to the lateral side of the body with an "S" hook and the urocyst lateral recessus are expanded, the cardinal ligaments can be exposed and be removed of 3/4. But part of the inferior of these ligaments should be preserved. The paracolpium are resected about 2 cm, 2 - 3 cm tissue of the vagina is removed. RESULTS: Compare with the control group, the urinary tract complications of the study group were significantly reduced (51.1% versus 23.0%, P < 0.01). There were a shorter surgical duration [(132 ± 20) min], less of the hemorrhage [(322 ± 100) ml] and blood transfusion [(154 ± 79) ml] in the study group than those in the control group (all P < 0.05). While, there was no significant difference at the survival rates of 5 years between the two groups (87.8% versus 88.6%, P = 0.793). CONCLUSION: The modified Piver class III hysterectomy is effective and applicable for patients with cervical cancer.