EPB41L3 Inhibits the Progression of Cervical Cancer Via the ERK/p38 MAPK Signaling Pathway.

This study was aimed to uncover the character and potential regulatory mechanism of EPB41L3 in cervical cancer (CC). CC cells were injected into BALB/c nude mice (female) to construct a xenograft tumor model. Real-time quantitative polymerase chain reaction (qRT-PCR) and western blot were performed to evaluate the expression of EPB41L3, ERK/p38 MAPK signal markers in CC tissues and cells. Cell counting kit-8 (CCK-8) and Transwell was applied to analyze the viability, invasion, and migration of CC cell lines. EPB41L3 was substantially decreased both in CC tissues and cells. Cell viability, invasion, and migration of CC cells were reduced by overexpressing EPB41L3. Bioinformatics analysis prerdicted that EPB41L3 was strongly related to the ERK/p38 MAPK pathway. Compared with Ad-nc mice, the volume and weight of tumors and ERK/p38 MAPK signal markers were down-regulated in Ad-EPB41L3 mice. After knocking down EPB41L3 with EPB41L3 siRNA (siEPB41L3), the ERK/p38 MAPK pathway was activated. Moreover, SB203580 treatment reversed the effect of EPB41L3 silencing on the improvement in viability, migration, and invasion of CC cells. EPB41L3 suppresses the progression of CC via activating the ERK/p38 MAPK pathway. EPB41L3 may serve as an effective therapeutic target for CC.

Prevalence, persistence, clearance and risk factors for HPV infection in rural Uyghur women in China.

BACKGROUND: The incidence of cervical cancer in Uyghur women ranks first among those in Han and other ethnic minority groups. We aimed to understand the natural history of HPV in Uyghur women. METHODS: A longitudinal cohort study on the natural history of HPV infection in rural Uyghur women in China was conducted between May 2013 and May 2014. A total of 11000 women from South Xinjiang underwent HPV screening by careHPV and liquid-based cytology. Ultimately, a total of 298 women with positive HPV and normal biopsy results or CIN1 were enrolled to participate in a study including follow-up HPV testing for two years. RESULTS: The HPV infection rate in Uyghur women was 9.15%. Among the participants, the careHPV test showed that 298 women were HPV-positive, and histology showed CIN1 or normal results for these women at baseline. Among these patients, after 24 months of initial recruitment, 92 (30.87%) patients had persistent HPV infections, and 206 (69.13%) had cleared HPV infection. Univariate analysis showed that persistent HPV infection was associated with age and shower frequency (P < 0.001 and P = 0.047, respectively). CONCLUSIONS: Our results suggest that women over the age of 50 years who have been infected with HR-HPV for more than 1 year should be regularly screened and monitored for HPV. In addition, education should be strengthened to improve poor health habits in these women.

Over-expression of EPB41L3 promotes apoptosis of human cervical carcinoma cells through PI3K/AKT signaling.

BACKGROUND: Cervical cancer is a significant malignancy of the female reproductive system. This study aimed to investigate the functions of Erythrocyte Membrane Protein Band 4.1 Like 3 (EPB41L3) in cervical cancer and to explore its underlying mechanisms. METHODS AND RESULTS: Expression of EPB41L3 in cervical cancer was analyzed by in-depth mining in The Cancer Genome Atlas (TCGA) clinical sequencing database. Patients with high expression of EPB41L3 had a good prognosis. EPB41L3 was overexpressed in HeLa and SiHa cells by a chemically synthesized lentivirus; its overexpression significantly inhibited cell proliferation, promoted apoptosis of HeLa and SiHa cells, and suppressed tumorigenesis in nude mice bearing HeLa cells. The results of microarray analysis showed that EPB41L3 overexpression led to marked gene expression changes, including 258 up-regulated genes and 168 down-regulated genes. Furthermore, EPB41L3 overexpression inhibited PI3K and AKT phosphorylation, leading to the apoptosis of cervical cancer cells. CONCLUSIONS: EPB41L3 overexpression inhibits cell proliferation, promotes apoptosis of cervical cancer cells, and suppresses tumorigenicity in vivo. Our findings suggest that EPB41L3 might be a new diagnostic biomarker and a therapeutic target for cervical cancer.

At what age should the Uyghur minority initiate cervical cancer screening if screened using careHPV.

BACKGROUND: The careHPV test as a primary screening method for cervical cancer has been proven to be the best option for Uyghur women in Xinjiang in a previous study. In this research, we aim to discuss the appropriate age for Uyghur women in Xinjiang to be screened for cervical cancer using careHPV. METHODS: Eleven thousand women aged 20-69 years old (mean age 38.93 ± 9.74) from South Xinjiang were screened using careHPV and liquid-based cytology, and the positive results were referred for colposcopy and cervical biopsy. A questionnaire regarding basic social characteristics, sexual practices, and reproductive history was administered to each woman. The age-specific prevalence of HPV positivity, cytology abnormality, and cervical intraepithelial neoplasia (CIN) 2+ in ≥25, ≥30, and ≥35 age groups were analyzed, and the diagnostic value of careHPV in the three age groups was evaluated. The chi-squared test was used to compare the differences between age groups. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve were calculated. RESULTS: The women were mostly married (76.3%) and delivered at 15-19 years of age (61.4%). The HPV infection rate was 9.15% and detection rates of CIN2+ and invasive cervical cancer were 1.53% (1530/100,000) and 0.25% (250/100,000), respectively. The first peak of HPV(+) appeared at the age of 30-34, while CIN2+ appeared at 35-39. CareHPV performed similarly well in the three age groups. CONCLUSION: Based on the results of our study, Uyghur women in Xinjiang should be recommended to initiate cervical cancer screening at the age of 30 years when screened using careHPV.

Human papillomavirus Posttreatment Clearance Time in Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer.

OBJECTIVE: The aim of the study was to determine an appropriate follow-up schedule for human papillomavirus (HPV) detection by evaluating the clearance time of HPV after treatment. MATERIALS AND METHODS: A retrospective study was conducted on 97 high-grade squamous intraepithelial lesion (HSIL) (cervical intraepithelial neoplasia 2-3) patients and 437 early invasive cervical cancer (CC) (stages Ia-IIa) patients who received radical surgery at the Affiliated Tumor Hospital of Xinjiang Medical University. Patient medical information, including personal information, pathological diagnosis, HPV infection status, and therapeutic methods, was obtained through the hospital's historical medical records management system. The clearance time of HPV was determined using Kaplan-Meier method analysis, and clearance time of HPV among different age groups, different grades, and different clinical stages were compared using the log-rank test. RESULTS: The median clearance time of all patients was 10.4 months. The median clearance time was longer in HSIL patients than in early invasive CC patients (p < .05). No statistical significance was found among different HSIL grades, CC stages, or patient age groups (P > 0.05). CONCLUSIONS: Delaying first posttreatment follow-up to 9 months in patients at high risk of noncompliance could potentially reduce burden of cost and repeated clinical visits. This follow-up approach could be consistently applied to all women regardless of age, severity, and extent of disease.

CDK6 3'UTR polymorphisms alter the susceptibility to cervical cancer among Uyghur females.

AIMS: Cyclin dependent kinase 6 (CDK6) plays a crucial role in malignant tumor whereas less is reported in cervical cancer development. The aim of this study was to evaluate the effects of CDK6 3' untranslated region (3'UTR) polymorphisms on cervical cancer susceptibility among Uyghur females. METHODS: The genotypes of the six CDK6 variants (rs8179, rs42032, rs42033, rs42034, rs42035, and rs42038) were identified among 306 cervical cancer cases and 310 healthy controls with the Agena MassARRAY platform. The associations of the candidate single nucleotide polymorphisms (SNPs) with the cervical cancer risk were evaluated under genetic models using conditional logistic regression analysis. Bioinformatics analysis was performed for SNP function prediction with the online databases. The expression differences between tumor tissues and normal cervix samples were also examined by Real-time PCR. RESULTS: CDK6 rs8179 and rs42033 were correlated to the decreased risk of cervical cancer in Uyghurs under the allele model (rs8179 and rs42033: OR = 0.60, 95% CI: 0.37-0.99, p = 0.043) and log-additive model (rs8179 and rs42033: OR = 0.62, 95% CI: 0.38-1.00, p = 0.047). Rs8179, rs42032, and rs42033 were associated with susceptibility to high-grade cervical cancer in different genetic models as well (p < 0.05). Dataset-based analysis also uncovered the potential effects of these significant SNPs. In addition, aberrant expression of CDK6 were detected in cervical tumors. CONCLUSIONS: Our results suggested the relationships between CDK6 3'UTR polymorphisms and cervical cancer pathogenesis, and the involvement of CDK6 in cervical cancer development among Uyghur females.

Serum Se, Ni, and As are associated with HPV infection and CIN2+ among Uyghur women in rural China.

BACKGROUND: Cervical cancer incidence and mortality is high in Uyghur ethnics. Their life style and dietary habit were different from other ethnics living together. Study on the role of trace elements in HPV infection and cervical lesion of Uyghur minority is needed for future intervention and prevention work. METHODS: In total, 833 Uyghur women were randomly selected from the screening site and hospital. The concentrations of the trace elements As, Fe, Cd, Ni, Cu, Zn, Mn, and Se were determined by atomic absorption spectrophotometry and inductively coupled plasma atomic emission spectroscopy. Univariate analysis was performed with chi-squared test between the HPV-positive and HPV-negative groups and between the case group and the control group. Multivariate analysis was performed with logistic regression. RESULTS: An As concentration ≥ 0.02 mg/kg was a risk factor for HPV infection (OR > 1, P < 0.05), and Ni concentration ≥ 0.1232 mg/kg and Se concentration ≥ 0.02 mg/kg were protective factors (OR < 1, P < 0.05). Concentrations of Fe ≥ 6.9153 mmol/L and As ≥0.02 mg/kg were risk factors for CIN2+ (OR > 1, P < 0.05), and concentrations of Ni ≥0.0965 mg/kg and Se ≥0.02 mg/kg were protective factors (OR < 1, P < 0.05). CONCLUSIONS: Low serum concentrations of Se and Ni and a high serum concentration of As might be related to HPV infection and CIN2+ in Uyghur women in rural China.