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.

LncRNA HOTAIR enhances RCC2 to accelerate cervical cancer progression by sponging miR-331-3p

Purpose Long noncoding RNAs (lncRNAs) have been gradually regarded as influential indicators of various cancers. The present study aimed to identify the effects of lncRNA HOTAIR on cervical cancer progression. Methods RNA and protein expressions were quantified by RT-qPCR and western blot assays. Fluorescence in situ hybridization (FISH) assay was carried out to examine the intracellular location of HOTAIR. Cancer cell viability and mobility were detected by CCK-8, colony formation, transwell and wound healing assays. Binding relationships between miR-331-3p and HOTAIR/RCC2 were validated by luciferase reporter assay. Results RT-qPCR assays showed that HOTAIR levels were notably upregulated in cervical cancer tissues and cell lines. Furthermore, a fluorescence in situ hybridization (FISH) assay suggested that HOTAIR was mostly located in the cytoplasm of cancer cells, indicating a sponging function. CCK-8, colony formation, Transwell and wound-healing assays indicated that knockdown of HOTAIR in HeLa and SiHa cells significantly reduced cell growth, migration and invasion. Subsequently, miR-331-3p was proven to be the target molecule of HOTAIR. In addition, results from Pearson's correlation analysis indicated negative correlation between HOTAIR and miR-331-3p in cervical cancer tissues. HOTAIR negatively modulated miR-331-3p expression. Ultimately, the target gene of miR-331-3p was verified to be RCC2, and miR-331-3p negatively modulated RCC2 expression. In addition, analysis on clinical cervical cancer tissues confirmed the negative correlation between miR-331-3p and RCC2. HOTAIR and RCC2 showed oncogenic functions in HeLa and SiHa cells, while miR-331-3p exerted the reverse effect. Conclusions HOTAIR plays a carcinogenic role in cervical cancer by targeting the miR-331-3p/RCC2 axis (AU)

LncRNA HOTAIR enhances RCC2 to accelerate cervical cancer progression by sponging miR-331-3p.

PURPOSE: Long noncoding RNAs (lncRNAs) have been gradually regarded as influential indicators of various cancers. The present study aimed to identify the effects of lncRNA HOTAIR on cervical cancer progression. METHODS: RNA and protein expressions were quantified by RT-qPCR and western blot assays. Fluorescence in situ hybridization (FISH) assay was carried out to examine the intracellular location of HOTAIR. Cancer cell viability and mobility were detected by CCK-8, colony formation, transwell and wound healing assays. Binding relationships between miR-331-3p and HOTAIR/RCC2 were validated by luciferase reporter assay. RESULTS: RT-qPCR assays showed that HOTAIR levels were notably upregulated in cervical cancer tissues and cell lines. Furthermore, a fluorescence in situ hybridization (FISH) assay suggested that HOTAIR was mostly located in the cytoplasm of cancer cells, indicating a sponging function. CCK-8, colony formation, Transwell and wound-healing assays indicated that knockdown of HOTAIR in HeLa and SiHa cells significantly reduced cell growth, migration and invasion. Subsequently, miR-331-3p was proven to be the target molecule of HOTAIR. In addition, results from Pearson's correlation analysis indicated negative correlation between HOTAIR and miR-331-3p in cervical cancer tissues. HOTAIR negatively modulated miR-331-3p expression. Ultimately, the target gene of miR-331-3p was verified to be RCC2, and miR-331-3p negatively modulated RCC2 expression. In addition, analysis on clinical cervical cancer tissues confirmed the negative correlation between miR-331-3p and RCC2. HOTAIR and RCC2 showed oncogenic functions in HeLa and SiHa cells, while miR-331-3p exerted the reverse effect. CONCLUSIONS: HOTAIR plays a carcinogenic role in cervical cancer by targeting the miR-331-3p/RCC2 axis. Moreover, clinical cervical cancer tissues confirmed the negative correlation between miR-331-3p with lncRNA HOTAIR and RCC2. These data suggested an underlying therapeutic target for cervical cancer.

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.