Ability Of Cervical Cancer Cells Research Articles

LncRNA HCP5 enhances the proliferation and migration of cervical cancer via miR-216a-5p/CDC42 axis.

To investigate the important roles of the cancer-promoting long non-coding RNAs (lncRNAs) in cervical cancer, the up-regulated lncRNAs and prognostic analysis were identified through Lnc2Cancer and Lncar. LncRNA-regulated miRNA and miRNA-target mRNA were analyzed based on starBase v2.0 and miTarbase to predict the lncRNA-miRNA-mRNA ceRNA network. Based on the above findings, the abnormally expressed histocompatibility leukocyte antigen complex P5 (HCP5) was identified in 31 cervical cancer patients through RT-qPCR. The stable cell lines were constructed to explore the effect of HCP5 on the promotion of cervical cancer and the regulatory role on the expression of miR-216a-5p and CDC42. Cell Counting Kit-8 (CCK8) assay, cell clone formation, and transwell assay were used to examine proliferation and migration ability of cervical cancer cells. The results displayed that the overexpression of HCP5 promoted cervical cancer cell proliferation and migration in vitro, and the elevated HCP5 can also promote tumor growth in vivo. Besides, RT-qPCR and western blot assay revealed that elevated HCP5 suppressed miR-216a-5p expression and then up-regulated the expression of CDC42. In contrast, knocking down HCP5 resulted in increased expression of miR-216a-5p and then downregulated the expression of CDC42. Rescue experiments also demonstrated that miR-216a-5p could in part intercept in promotion impact caused by HCP5 on cervical cancer cells. Above all, HCP5, as an oncogene, can promote proliferation and migration ability of cervical cancer via the regulation of the miR-216a-5p/CDC42 axis.

Identification of miR-885-5p as a Tumor Biomarker: Regulation of Cellular Function in Cervical Cancer

Objectives: MicroRNAs were revealed as biomarkers for early detection or prognosis predictors of cancer and were involved in the progression of cancer. The present study investigated the expression pattern and potential clinical and functional role of miR-885-5p in cervical cancer. Design: A total of 115 pairs of cervical cancer tissue specimens and adjacent nontumor paracancerous tissue specimens were collected from the cervical cancer patients who underwent surgical resection or biopsy without preoperative systemic therapy at Maternity and Child Health Care of Zaozhuang from 2012 to 2014. Participants/Materials, Setting, Methods: The expression levels of miR-885-5p in cervical cancer were measured using the qRT-PCR assay. A follow-up study was conducted, and the Kaplan-Meier method with log-rank test was used to analyze the potential clinical significance of miR-885-5p in cervical cancer. The functional experiments including CCK-8, Transwell migration, and invasion assays were used to investigate the biological function of miR-885-5p in cervical cancer cells. Results: miR-885-5p expression was decreased in tumor tissues and tumor cell lines compared to normal control. Low expression of miR-885-5p was related to lymph node metastasis, late FIGO stage, and shorter overall survival outcome. Ascending expression of miR-885-5p inhibited the proliferative, migratory, and invasive abilities of cervical cancer cells, while downregulation of miR-885-5p promoted these cellular abilities of cervical cancer cells in vitro. Limitations: The patient population size was limited; thus, the clinical significance of miR-885-5p requires further verification. Second, the precise mechanism of miR-885-5p in cervical cancer is still exclusive. In the future studies, a larger sample size will be required to confirm the prognostic value of miR-885-5p in cervical cancer, and the possible targets, as well as the detailed mechanism of miR-885-5p, will be investigated. Conclusions: miR-885-5p expression was decreased in cervical cancer, and downregulation of miR-885-5p promoted the progression of cervical cancer cells. MiR-885-5p may be an independent prognostic predictor and therapeutic target for treating cervical cancer.

FABP4 is an independent risk factor for lymph node metastasis and poor prognosis in patients with cervical cancer

BackgroundPelvic lymph node metastasis (LNM) is a crucial independent prognostic factor in cervical cancer (CCa) and serves as an indicator for radiation therapy as the primary or an adjuvant treatment option. However, preoperative diagnosis of LNM remains challenging. Thus, we aimed to identify biomarkers of LNM in patients with presumed early-stage CCa.MethodsThe differentially expressed genes (DEGs) between tumours with different lymph node statuses were identified by using The Cancer Genome Atlas database. Then, univariate Cox regression analysis and Kaplan–Meier analyses were utilized to screen overall survival (OS)-associated genes. Multivariate Cox analysis and logistical analysis were utilized to evaluate independent risk factors for OS and LNM, respectively. Subsequently, the protein level of fatty acid binding protein 4 (FABP4) was detected in normal cervical and CCa tissues by immunohistochemistry assays. EdU assays were performed to determine whether FABP4 altered the proliferation of cervical cancer cells. Wound healing and Transwell assays were conducted to explore the effects of FABP4 depletion on migratory and invasive abilities of cervical cancer cells. F-actin fluorescence staining were performed to investigate morphological change and Western blotting analyses were performed to determine epithelial mesenchymal transition-related marker expression and downstream signalling pathways.ResultsA total of 243 DEGs, including 55 upregulated and 188 downregulated DEGs, were found in CCa patients with LNM versus those without LNM. Among these, FABP4 was found to be closely associated with poor OS. Multivariate analysis uncovered that FABP4 was an independent risk factor for OS and LNM in patients with CCa. The immunohistochemical results verified dramatically increased FABP4 expression in CCa tissues compared to normal cervical epithelia and its association with poor OS and LNM. In vitro, The proliferation, migration and invasion of cervical cancer cells were significantly inhibited after knocking down of FABP4, which was accompanied by elevated expression of E-cadherin and downregulated expression of N-cadherin, Vimentin and p-AKT.ConclusionsFABP4 might be a promising biomarker of LNM and survival in patients with early-stage CCa and therefore could significantly contribute to the development of personalized prognosis prediction and therapy optimization.

CircASAP1 promotes the development of cervical cancer through sponging miR-338-3p to upregulate RPP25.

Circular RNAs have been identified as vital regulators to regulate the development of human cancers, including cervical cancer. Therefore, this study was designed to clarify the underlying mechanism of circASAP1 in cervical cancer. The real-time quantitative PCR assay was applied to quantify the expression levels of circASAP1, microRNA (miR)-338-3p, and ribonuclease P and MRP subunit p25 (RPP25) in cervical cancer tissues and cells. The cell proliferation ability was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide and colony-forming assays. The protein expression levels of cyclin D1, proliferating cell nuclear antigen, and RPP25 were assessed by western blot assay. Flow cytometry assays were used to determine the apoptosis and cell cycle distribution of cervical cancer cells. The transwell assay was employed to test the migration and invasion abilities of cervical cancer cells. The interaction relationship between miR-338-3p and circASAP1 or RPP25 was confirmed by dual-luciferase reporter assay and RNA pull-down assay. The xenograft experiment was established to clarify the functional role of circASAP1 inhibition in vivo. CircASAP1 was overexpressed in cervical cancer tissues and cells compared with negative groups. Additionally, the loss-of-functional experiments implied that knockdown of circASAP1 impeded proliferation, migration, and invasion while induced apoptosis and cell cycle arrest in cervical cancer cells along with repressed tumor growth in vivo through regulation of miR-338-3p. In addition, RPP25 was a target mRNA of miR-338-3p, and overexpression of miR-338-3p suppressed proliferation, migration, and invasion while induced apoptosis and cell cycle arrest in cervical cancer cells by suppressing RPP25 expression. Mechanistically, circASAP1 could function as a sponge for miR-338-3p to increase the expression of RPP25, and further regulated proliferation, migration, invasion, apoptosis, and cell cycle program of cervical cancer cells, which might be potential markers for cervical cancer diagnosis.

MiR-186-3p attenuates tumorigenesis of cervical cancer by targeting IGF1

BackgroundMounting evidence in the cancer literature suggests that microRNAs (miRNAs) influence the progression of human cancer cells by targeting protein-coding genes. How insulin-like growth factor 1(IGF1) and miR-186-3p contribute to the development of cervical cancer (CC) remains unclear. This study examined the regulatory roles of miR-186-3p and IGF1 in CC development.MethodsGene expression levels were determined by qRT-PCR. Proliferation, migration, and apoptosis of CC and normal cells were determined by MTT, Transwell, and caspase-3 activity assays, respectively. Dual-luciferase reporter activity and RNA pull-down assays were performed to identify the target gene of miR-186-3p.ResultsIGF1 was the target of miR-186-3p. The expression of miR-186-3p inhibited cell proliferation and migration abilities of CC cell lines, but induced the apoptosis rate of CC cells. IGF1 could restore the inhibitory effects of miR-186-3p on the proliferation, migration, and apoptosis abilities of CC cells. Experimental results revealed that miR-186-3p could inhibit IGF1 expression, thereby reducing the viability of CC cells.ConclusionsThe data suggest that targeting of IGF1 by miR-186-3p could be crucial in regulating the progression of CC.

Constructe a novel 5 hypoxia genes signature for cervical cancer

BackgroundHypoxia, which affects the development, metastasis and prognosis of cancer, represents a key feature of cancer. This study describe a hypoxia risk factor model, with predicting the prognosis of cervical cancer.MethodsBased on hypoxia pathway related genes, we divided cervical cancer samples into high and low expression groups. A cox analysis was then performed. Genes from these cervical cancer samples showing a significant impact on OS were selected for cluster analysis to obtain two subtypes. The TPM dataset of TCGA was divided into training and validation sets. For the training set, a lasso analysis was conducted as based on cox analysis of meaningful genes and a risk factor model was constructed. The constructed model was verified in internal and external data sets. Finally, RT-PCR, immunohistochemistry were used to detect the expression of relative genes or proteins and functional assays were used to evaluate the biological function of signature genes.ResultsTwo molecular subtypes were obtained, Cluster2 vs Cluster1.These subtypes were obtained by clustering with a total of 149 DEGs (Differential expressed genes) being in line with this standard, of which 27 were up-regulated and 122 were down-regulated. The five genes with lambda = 0.0571 were selected to construct the model, the RiskScore = AK4*0.042 + HK2*0.021 + P4HA1*0.22 + TGFBI*0.1 + VEGFA*0.077. Further, in order to verify the signature, we used TCGA-test and GSE44001 chip datasets to test, and finally got a good risk prediction effect in those datasets. Moreover, the result of RT-PCR and immunohistochemistry demonstrated that AK4, HK2, P4HA1, TGFBI and VEGFA were all highly expressed in these cervical cancer tissue samples. The functional study shown that expression of AK4, HK2, P4HA1, TGFBI and VEGFA can regulate the proliferation, migration, and invasion ability of cervical cancer cells in vitro.ConclusionsIn summary, we developed a 5-gene signature prognostic hierarchical system based on the hypoxic pathway of cervical cancer, which is independent of clinical characteristics. And also conducted experimental verifications on these signature gene. Therefore, we propose that use of this classifier as a molecular diagnostic test can provide an effective means for evaluating the prognostic risk of cervical cancer patients, and provide potential targets for the treatment of cervical cancer patients.

MiR-92a promotes cervical cancer cell proliferation, invasion, and migration by directly targeting PIK3R1.

ObjectiveTo clarify the role of miR‐92a in regulating the malignant progression of cervical cancer and its specific molecular mechanism.MethodsqRT‐PCR was used to detect the differential expression of miR‐92a in cervical cancer and adjacent tissues. The effects of overexpression of miR‐92a on the proliferation, migration, and invasion of HeLa and SiHa cells were tested. Luciferase assays and rescue experiments were used to investigate the regulatory mechanism of miR‐92a on its downstream gene PIK3R1 and their interaction in the progression of cervical cancer.ResultsmiR‐92a was significantly up‐regulated in cervical cancer tissues. Overexpression of miR‐92a significantly increased the ability of cervical cancer cells to proliferate, migrate, and invade. PIK3R1 was identified as a downstream gene of miR‐92a. In cervical cancer tissues, PIK3R1 was found to be down‐regulated and negatively correlated with the level of miR‐92a. Overexpression of PIK3R1 reversed the promotional effect of overexpressed miR‐92a on the proliferation, migration, and invasion of cervical cancer.ConclusionmiR‐92a is up‐regulated in cervical cancer tissues. miR‐92a promotes the malignant development of cervical cancer by negatively regulating PIK3R1.

RPL34‐AS1–induced RPL34 inhibits cervical cancer cell tumorigenesis via the MDM2‐P53 pathway

Ribosomal proteins (RPs) are important components of ribosomes and related to the occurrence and development of tumors. However, little is known about the effects of the RP network on cervical cancer (CC). In this study, we screened differentially expressed RPL34 in CC by high‐throughput quantitative proteome assay. We found that RPL34 acted as a tumor suppressor and was downregulated in CC and inhibited the proliferation, migration, and invasion abilities of CC cells. Next, we verified that RPL34 regulated the CC through the MDM2‐P53 pathway by using Act D medicine, MDM2 inhibitor, and a series of western blotting（WB）assays. Moreover, an antisense lncRNA, RPL34‐AS1, regulated the expression of RPL34 and participated in the tumorigenesis of CC. RPL34 can reverse the effect of RPL34‐AS1 in CC cells. Finally, by RNA‐binding protein immunoprecipitation (RIP) assay we found that eukaryotic initiation factor 4A3 (EIF4A3), which binds to RPL34‐AS1, regulated RPL34‐AS1 expression in CC. Therefore, our findings indicate that RPL34‐AS1–induced RPL34 inhibits CC cell proliferation, invasion, and metastasis through modulation of the MDM2‐P53 signaling pathway, which provides a meaningful target for the early diagnosis and treatment of CC.

Clinical significance of miR-1298 in cervical cancer and its biological function in vitro.

Cervical cancer is one of the most malignant tumors in women. miR-1298 was reported to be abnormally expressed and serve crucial role in tumorigenesis of several types of cancer; however, the role of miR-1298 in cervical cancer remains unknown. The present study aimed to evaluate the clinical and biological significance of miR-1298 in cervical cancer. To do so, the expression level of miR-1298 in cervical cancer tissues and cells was evaluated by reverse transcription quantitative PCR. Kaplan-Meier survival analysis and Cox regression analysis were used to explore the prognostic significance of miR-1298 in patients with cervical cancer. Cell Counting Kit-8 and Transwell migration and invasion assays were used to evaluate the effect of miR-1298 on the proliferative, migratory and invasive abilities of cervical cancer cells, respectively. The expression of miR-1298 was lower in cancer tissues and cells compared with normal tissues and cells. Furthermore, miR-1298 expression was associated with lymph node metastasis, tumor diameter and staging from the International Federation of Gynecology and Obstetrics. In addition, patients with low miR-1298 expression had poorer overall survival. These findings suggested that miR-1298 may be considered as an independent prognostic factor for patients with cervical cancer. Furthermore, the results demonstrated that miR-1298 knockdown could promote tumor cell proliferation and migratory and invasive abilities. In addition, nucleus accumbens-associated 1 (NACC1) was demonstrated to be a direct target of miR-1298. Taken together, these findings indicated that miR-1298 overexpression may be considered as a prognostic biomarker for cervical cancer and that miR-1298 may play an inhibitor role in cervical cancer by targeting NACC1.

Downregulation of LncRNA DARS-AS1 Inhibits the Tumorigenesis of Cervical Cancer via Inhibition of IGF2BP3

BackgroundEvidence has been shown that long noncoding RNAs (lncRNAs) play an important role in the development of cervical cancer. Recently, lncRNA DARS-AS1 was reported to be dysregulated in several cancer types; however, the role of DARS-AS1 in cervical cancer remains unclear.MethodsFlow cytometry and transwell invasion assays were performed to determine the apoptosis and invasion in cervical cancer cells. In addition, RNA pull-down and fluorescence in situ hybridization (FISH) assays were conducted to assess the interaction between DARS-AS1 and IGF2BP3 in cervical cancer cells.ResultsDownregulation of DARS-AS1 significantly induced apoptosis and cell cycle arrest in cervical cancer cells. Meanwhile, the invasion ability of cervical cancer cells was inhibited by DARS-AS1 knockdown as well. RNA pull-down and FISH results showed that DARS-AS1 interacted with IGF2BP3. Mechanistically, DARS-AS1 positively regulated IGF2BP3 expression via stabilization of IGF2BP3 mRNA. Rescue assays confirmed that DARS-AS1 regulated the progression of cervical cancer through interacting with IGF2BP3 in vitro. In addition, in vivo experiments revealed that downregulation of DARS-AS1 inhibited tumor growth in SiHa xenograft model.ConclusionIn this study, we found that downregulation of DARS-AS1 could inhibit the growth of cervical cancer cells via inhibition of IGF2BP3, suggesting DARS-AS1 might serve as a potential target for the treatment of cervical cancer.

FAM83A Promotes the Proliferative and Invasive Abilities of Cervical Cancer Cells via Epithelial-Mesenchymal Transition and the Wnt Signaling Pathway.

The family with sequence similarity 83, member A (FAM83A) gene is associated with the occurrence and development of many malignant tumors. Our aim was to explore the role of FAM83A in cervical cancer. FAM83A was overexpressed or knocked down in cervical cancer cells, and the expressions of FAM83A, key proteins involved in the epithelial-mesenchymal transition (EMT), and Wnt signaling pathway-related proteins were detected by western blot analysis. Cell proliferative and invasive abilities were also examined using cell proliferation, colony formation, and Matrigel invasion assays. Cells were treated with the Wnt pathway inhibitor XAV-939 to determine whether Wnt signaling was necessary for the effect of FAM83A on cervical cancer cells. FAM83A was highly expressed in cervical cancer tissues and was associated with differentiation, TNM stage, lymph node metastasis, and poor prognosis in patients with cervical cancer. Knockdown of FAM83A inhibited the proliferation, colony formation, and invasion of cervical cancer cells. The opposite results were observed in FAM83A-overexpressing cells, and FAM83A overexpression also promoted EMT and Wnt signaling. XAV-939 reversed the activation of Wnt signaling and EMT induced by FAM83A. In conclusion, FAM83A expression was increased in cervical cancers and correlated with poor prognosis of patients. FAM83A overexpression can activate the Wnt signaling pathway, facilitate EMT, and promote the proliferative and invasive abilities of cervical cancer cells.

APMAP Promotes Epithelial-Mesenchymal Transition and Metastasis of Cervical Cancer Cells by Activating the Wnt/β-catenin Pathway.

Cervical cancer is a malignant tumor of the female reproductive system. At present, its occurrence, development and transfer mechanism are not entirely clear. APMAP (Adipocyte Plasma Membrane Associated Protein) is a glycosyl type II transmembrane protein that is mainly distributed in the plasma membrane and endoplasmic reticulum of adipocytes. APMAP has been reported to be involved in lipid transport and can induce epithelial-mesenchymal transition of prostate cancer and the liver metastasis of colorectal cancer. However, the role of APMAP in cervical cancer is still unknown. We analyzed the expression and prognosis of APMAP using data in both the GEO and the TCGA databases. We analyzed the function of APMAP using Transwell, wound healing assay and flow cytometry, and assessed the main mechanisms of APMAP by RT-PCR and Western blotting. We found that APMAP was highly expressed in cervical cancer tissues, and patients with high expression had poor prognosis. The functional in vitro experiments demonstrated that APMAP knockdown significantly inhibited the migration ability of cervical cancer cells, but had little effect on cell apoptosis. Mechanically, APMAP promotes cervical cancer cell migration and epithelial-mesenchymal transition by activating the Wnt/β-catenin pathway. Overall, APMAP is a potential prognostic marker as well as a therapeutic target of cervical cancer.

The promotion of cervical cancer progression by signal transducer and activator of transcription 1-induced up-regulation of lncRNA MEOX2-AS1 as a competing endogenous RNA through miR-143-3p/VDAC1 pathway

ABSTRACT Long non-coding RNAs (lncRNAs) are the new regulators and biomarkers for various tumors. However, in cervical cancer (CC), the potential roles of lncRNAs are not well characterized. This research aimed at exploring the roles of MEOX2 antisense RNA 1(MEOX2-AS1) in CC progression and the underlying mechanisms. The examination of MEOX2-AS1 levels in CC specimens and cell lines was conducted by RT-PCR. Loss-of-function experiments were performed for the assays of proliferation, migration, and invasion of CC cells after various treatments. Animal experiments were applied for the determination of the effects of MEOX2-AS1 in vivo. Bioinformatics analysis, together with dual-luciferase reporter assays, was applied to demonstrate the possible relationships among MEOX2-AS1, miR-143-3p and VDAC1. In the paper, we reported that MEOX2-AS1 levels were distinctly upregulated in CC cells and tissues, and higher MEOX2-AS1 expressions indicated a poor clinical outcome. Besides, STAT1 could activate transcriptions of MEOX2-AS1 by binding directly to its promoter region. The silence of MEOX2-AS1 suppressed the metastatic and proliferative ability of CC cells, as revealed by functional assays. Mechanistically, MEOX2-AS1 sponged miR-143-3p to regulate VDAC1 expressions. Furthermore, miR-143-3p inhibitor reversed the anti-proliferation and anti-metastasis effect of MEOX2-AS1 knockdown. Overall, the data indicated that the MEOX2-AS1/miR-143-3p/VDAC1 pathway participated in CC progression, making it a novel therapeutic target for CC cures.

Lipopolysaccharide Affects the Proliferation and Glucose Metabolism of Cervical Cancer Cells Through the FRA1/MDM2/p53 Pathway.

Previous studies have found that LPS and FRA1 play opposite roles in cervical cancer. In addition, LPS functions by regulating the expression of FRA1 in many disease models, but there is currently no study of their relationship in the energy metabolism of tumor cells. This study, therefore, investigates the effects of LPS on FRA1-mediated glucose metabolism and the possible mechanisms it may have in cervical cancer cells. We constructed FRA1 stable overexpressing/ empty vector cervical cancer cell lines, where glucose consumption, the level of lactic acid production and the expression of energy metabolism related molecules were detected under the stimulation of LPS. At the same time, the changes in proliferation ability of cervical cancer cells were detected. We discovered that LPS promotes glucose consumption, lactic acid production, pentose phosphate bypass, and inhibits aerobic oxidation, by inhibiting the expression of FRA1; and that LPS promotes the growth of cervical cancer cells. Our results indicate that LPS affects the proliferation and glucose metabolism of cervical cancer cells through the FRA1/MDM2/p53 pathway.

Long non-coding RNA KCNQ1OT1 facilitates the progression of cervical cancer and tumor growth through modulating miR-296-5p/HYOU1 axis

ABSTRACT Literature reports that lncRNA KCNQ1OT1 is markedly up-regulated in cervical cancer (CC) tissues and cell lines, and KCNQ1OT1 can promote the proliferation and metastasis of CC cells. This current work was designed to investigate the molecular mechanism underlying the participation of KCNQ1OT1 in CC progression. Herein, RT-qPCR was utilized for determining the levels of KCNQ1OT1, miR-296-5p and HYOU1 in clinical tumor tissue specimens and CC cell lines. Then, starBase predicted the complementary binding sites of KCNQ1OT1 and miR-296-5p or miR-296-5p and HYOU1. Dual-luciferase reporter assay/RIP assay validated the interplays among KCNQ1OT1/miR-296-5p/HYOU1. In addition, CCK-8, wound healing and transwell assays were employed to assess the proliferative, migrative and invasive properties of CC cells. Moreover, nude mice xenograft model was established by subcutaneously injection with SiHa cells in order to validate the precise functions of KCNQ1OT1/miR-296-5p/HYOU1 axis in CC in vivo. Besides, Immunohistochemical staining examined Ki-67 expression in xenograft tumors and western blotting analysis detected expressions of MMP2/9 and Wnt/β-catenin signaling pathway in CC cells and xenograft tumors. Elevated KCNQ1OT1 and HYOU1 as well as reduced miR-296-5p were observed in clinical tumor tissue specimens and CC cell lines. Results revealed that upregulation of miR-296-5p counteracted the enhancing effects of overexpressed KCNQ1OT1 on the proliferative, migrative and invasive abilities of CC cells. Additionally, HYOU1 overexpression abolished the suppressing effects of silenced KCNQ1OT1 on the malignant behaviors of CC cells and tumor growth. To conclude, KCNQ1OT1 could aggravate the malignant behaviors of CC and facilitate tumor growth through modulating miR-296-5p/HYOU1 axis.

Solute Carrier Family 5 Member 8 Inhibits the Proliferation and Migration and Promotes Apoptosis of Cervical Cancer Cells by Upregulating CCAAT/Enhancer Binding Protein Delta

SLC5A8 has been studied in a variety of cancers as an anti-tumor factor. SLC5A8 is down-regulated in cervical cancer (CC), but its specific role in CC has not been reported. The expression of SLC5A8 and CEBPD was detected by RT-qPCR and western blot. Subsequently, cell viability was detected by CCK-8 technology and cell proliferation level was detected by cloning formation assay. The ability of CC cells was detected by Transwell assay.Wound healing detected cell migration. Cell apoptosis was detected by flow cytometry. The expression of apoptosis-related proteins bcl-2, Bax, caspase3 and caspase9 were detected by western blot. In addition, the immunoprecipitation technique detected the association between SLC5A8 and CEBPD. The results showed that the expression of SLC5A8 in CC cell lines was significantly decreased. After overexpression of SLC5A8, we found that the proliferation level of Hela increased, cell survival rate, invasion and migration ability decreased, and cell apoptosis increased. The expression of CEBPD in CC cells is also decreased. In addition, we found that SLC5A8 has a targeted regulatory effect on CEBPD. It interfered with the expression of CEBPD and inhibited the effect of overexpression of SLC5A8 on the proliferation, invasion, migration and apoptosis of Hela in CC. In conclusion, overexpression of SLC5A8 inhibited the proliferation, migration of CC cells and promoted apoptosis by upregulating the expression of CEBPD.

Human Papillomavirus E7 Oncoprotein Promotes Proliferation and Migration through the Transcription Factor E2F1 in Cervical Cancer Cells

High-Risk Human Papillomavirus (HR-HPV) persistent infection is the main cause of cervical cancer and its precancerous lesions. A previous study showed that HPV16 and HPV58 infections were the most common infection types in the local region. Some studies also declared that HPV58 E7 variants increased the risk of cervical cancer among Asian populations. This study aimed to determine whether the HPV58 E7 T20I (C632T) variant promotes the malignant behavior of cervical cancer cells and the underlying mechanism of the HR-HPV E7 oncoprotein involved in the development of cervical cancer. CCK-8 and clone formation assays were used to detect cell proliferation ability. Transwell assays and cell wound healing assays were used to evaluate cell migration ability. Targeted knockdown of E2F1 expression using specific siRNA, RT-qPCR and Western blot were performed to assess gene expression changes. A chromatin immunoprecipitation assay was used to verify that E2F1 interacted with the TOP2A promoter region. HPV58 E7 and HPV58 E7M oncoproteins increased the proliferation and migration ability of cervical cancer cells. However, the HPV58 E7 T20I variant did not promote malignant behaviors compared with wildtype HPV58 E7. HPV E7 and E7M oncoproteins increased the expression of TOP2A, BIRC5 and E2F1, and knockdown of HPV E7 decreased their expression. Low E2F1 expression reduced the expression of TOP2A and BIRC5 and inhibited the proliferation and migration ability of cervical cancer cells. E2F1 interacted with the TOP2A gene promoter region to promote its transcriptional expression. The HPV58 E7 T20I variant did not promote malignant behaviors compared with wild-type HPV58 E7. The HR-HPV E7 oncoprotein enhanced the proliferation and migration of cervical cancer cells, which was considered to be due to the HPV E7 oncoprotein, increasing the expression of BIRC5 and TOP2A by upregulating the transcription factor E2F1.

MiR-196a targeting LRIG3 promotes the proliferation and migration of cervical cancer cells

In recent years, studies have found that miR-RNA plays a role in cell proliferation, differentiation, apoptosis and metabolism. Among them, miR-196a is closely related to cervical cancer. Therefore, this experiment investigates the effect of mir-196a expression on cervical cancer cells and related mechanisms. The expression level of miR-196a in the cervical cancer cell line was assayed with the RT-PCR method, and liposome transfection was used to investigate its up-regulation or down-regulation in cervical cancer cells. The CCK-8 method and flow cytometry were used to measure cervical cancer cell proliferation and apoptosis, while the Transwell assay was used to determine cell migration and invasion of each transfection group. Bioinformatics was used to predict the target gene of miR-196a, which was verified using dual luciferase report experiment and Western blot, and miR-196a was further transfected with si-LRIG3 to detect its reversal effect on miR-196a regulation. Inhibition of the expression of miR-196a significantly reduced the proliferation, migration and invasion of cervical cancer cells, and promoted their apoptosis. Results from dual luciferase assay showed that miR-196a and LRIG3 had direct targeting effects. Cell proliferation, migration and invasion were enhanced by a reduction in the expression level of LRIG3 protein after miR-196a inhibitor cells were transfected with si-LRIG3. The expression of miR-196a is up-regulated in cervical cancer, and it promotes the growth of cervical cancer by its targeting effect on LRIG3 expression, resulting in enhancement of the proliferation, migration and invasion ability of cervical cancer cells, and inhibition of apoptosis.

MicroRNA‑130a‑3p promotes the proliferation and inhibits the apoptosis of cervical cancer cells via negative regulation of RUNX3.

Aberrant expression of microRNAs (miRs) has been reported in various types of cancer. The aim of the present study was to investigate the role and underlying molecular mechanism of miR‑130a‑3p in cervical cancer (CC). The expression of miR‑130a‑3p in CC tissues and cell lines (CaSki and SiHa) was measured via reverse transcription‑quantitative PCR. SiHa and CaSki cells were transfected with miR‑130a‑3p mimics and a miR‑130a‑3p inhibitor, respectively. The proliferation, apoptosis and migration and invasion abilities of CC cells were then measured using MTT, flow cytometry, wound‑healing and Transwell assays, respectively. TargetScan and dual‑luciferase reporter gene assays were performed to analyze the association between miR‑130a‑3p and its predicted target gene Runt‑related transcription factor 3 (RUNX3). In addition, a xenograft tumor model was established in mice to evaluate the impact of miR‑130a‑3p on tumor growth invivo. The expression of miR‑130a‑3p was markedly upregulated in CC tissues and cell lines compared with normal tissues and cells. Transfection with miR‑130a‑3p mimics significantly promoted the proliferation, migration and invasion, and inhibited the apoptosis of SiHa cells. Treatment of CaSki cells with a miR‑130a‑3p inhibitor resulted in opposite effects to those of miR‑130a‑3p mimics. RUNX3 was identified as the target gene of miR‑130a‑3p, and overexpression of RUNX3 eliminated the tumor‑promoting effect of miR‑130a‑3p mimics on CC cells. Overexpression of miR‑130a‑3p also promoted tumor growth in mice. In conclusion, miR‑130a‑3p promoted proliferation, migration and invasion, and inhibited the apoptosis of CC cells via targeting RUNX3, suggesting a novel treatment target for CC.

Dioscorea nipponica Makino suppresses TPA-induced migration and invasion through inhibition of matrix metalloproteinase-9 in human cervical cancer cells.

Dioscorea nipponica Makino has been used for the treatment of chronic bronchitis, rheumatoid arthritis, cough, and asthma. Several studies have established the antitumor effect of D. nipponica Makino extract (DNE). However, no investigations have considered the antimetastatic potential of DNE in cervical cancer cells. The present study examined the effects of DNE on cervical cancer cells treated with 12-O-tetradecanoylphorbol-13-acetate and characterized the possible molecular mechanisms. MTT assay results indicated that DNE exhibited very low cytotoxicity, and DNE significantly reduced the invasion and migration abilities of cervical cancer cells. Gelatin zymography analysis revealed that DNE significantly inhibited matrix metalloproteinase-9 (MMP-9) activity. Reverse transcription-polymerase chain reaction assay results revealed that DNE treatment inhibited the MMP-9 mRNA levels of HeLa and SiHa cells. Western blot results revealed that DNE significantly diminished the ERK1/2 phosphorylation. In conclusion, we revealed that the antimetastatic effects of DNE on cervical cancer cells are due to its inhibition of MMP-9 expression through the ERK1/2 pathway.