Five new flavonoids and their pharmacological activities from Iris tenuifolia Pall.

Five new components including two new isoflavones, 5, 7, 2', 3'-tetrahydroxy-6-methoxyisoflavone (1), 5, 7, 2', 3'-tetrahydroxy-8-methoxyisoflavone (2), one flavonol 5, 3', 4'-tetrahydroxy-7, 2'-dimethoxyflavonol (3), one flavanone (2S)-5, 7, 3'-trihydroxy-2'-methoxyflavanone (4), and one flavanonol (2R, 3R)-3, 5, 3', 4'-tetrahydroxy-7, 2'-dimethoxyflavanonol (5), along with nine known flavonoids (6-14) were isolated from under ground parts of Iris tenuifolia Pall.. Their structures were elucidated by NMR and HRESIMS data and by comparison of CD spectra with compounds having similar structure. The separated compounds were evaluated for in vitro antioxidant activities by DPPH and ABTS. The α-glucosidase inhibitory activity of the compounds were evaluated with the pNPG method, the results indicated flavonoids were potential inhibitors of α-glucosidase. Moreover, in vitro anti-oxidative assay using flow cytometry indicated that compounds 1-5 showed strong oxidation resistance ability on C8D1A cells without affecting the cell viability.

Identification of Bromophenols' glucuronidation and its induction on UDP- glucuronosyltransferases isoforms.

Bromophenols (BPs) are prominent environmental pollutants extensively utilized in aquaculture, pharmaceuticals, and chemical manufacturing. This study aims to identify UDP- glucuronosyltransferases (UGTs) isoforms involved in the metabolic elimination of BPs. Mono-glucuronides of BPs were detected in human liver microsomes (HLMs) incubated with the co-factor uridine-diphosphate glucuronic acid (UDPGA). The glucuronidation metabolism reactions catalyzed by HLMs followed Michaelis-Menten or substrate inhibition kinetics. Recombinant enzymes and inhibition experiments with chemical reagents were employed to phenotype the principal UGT isoforms participating in BP glucuronidation. UGT1A6 emerged as the major enzyme in the glucuronidation of 4-Bromophenol (4-BP), while UGT1A1, UGT1A6, and UGT1A8 were identified as the most essential isoforms for metabolizing 2,4-dibromophenol (2,4-DBP). UGT1A1, UGT1A8, and UGT2B4 were deemed the most critical isoforms in the catalysis of 2,4,6-tribromophenol (2,4,6-TBP) glucuronidation. Species differences were investigated using the liver microsomes of pig (PLM), rat (RLM), monkey (MyLM), and dog (DLM). Additionally, 2,4,6-TBP effects on the expression of UGT1A1 and UGT2B7 in HepG2 cells were evaluated. The results demonstrated potential induction of UGT1A1 and UGT2B7 upon exposure to 2,4,6-TBP at a concentration of 50 µM. Collectively, these findings contribute to elucidating the metabolic elimination and toxicity of BPs.

Clinical Performance of a Dedicated Urine-Based Assay for the Detection of Human Papillomavirus and Cervical Intraepithelial Neoplasia.

Objective: The objective of this study is to assess the clinical performance of a urine-based high-risk human papillomavirus (hrHPV) test for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). Methods: Between September and December 2021, women aged 20 to 65 years referred to colposcopy clinic were prospectively recruited at three clinical centers in China. Paired urine and cervical specimens from all enrolled women were obtained for hrHPV DNA fluorescence quantitative PCR test. The results of liquid-based cytology (LBC), colposcopy and diagnostic biopsies were collected. We evaluated the sensitivity and specificity for CIN and assessed the agreement/kappa value. Results: A total of 732 women (median age, 40 years) with valid results were included in the study, and 130 (17.8%) women were histologically confirmed as CIN2+. The sensitivity of urine and cervical test for CIN2+ and CIN3+ were 87.69% and 85.45%, respectively. The specificity of urine test performed better than cervical test in women with

High-fat diet promotes tumor growth in the patient-derived orthotopic xenograft (PDOX) mouse model of ER positive endometrial cancer.

Endometrial cancer, one of the common gynecological malignancies, is affected by several influencing factors. This study established a unique patient-derived orthotopic xenograft (PDOX) nude mouse model for the study of influencing factors in ER positive endometrial cancer. The aim of this study was to demonstrate that a high-fat diet can affect the growth of ER positive endometrial cancer PDOX model tumors. The tumor tissues were expanded by subcutaneous transplantation in nude mice, and then the subcutaneous tumor tissues were orthotopically implanted into the nude mouse uterus to establish the PDOX model. After modeling, they were divided into high-fat diet group and normal diet group for 8 weeks of feeding, which showed that high-fat diet significantly promoted tumor growth (P < 0.001) and increased the protein expression level of ERα in tumor tissues. This study demonstrates that PDOX models of endometrial cancer can embody the role of dietary influences on tumor growth and that this model has the potential for preclinical studies of cancer promoting factors.

EphA2 Promotes the Development of Cervical Cancer through the CXCL11/PD-L1 Pathway.

Erythropoietin-producing hepatoma receptor A2 (EphA2), receptor tyrosine kinase, the most widespread member of the largest receptor tyrosine kinase family, plays a critical role in physiological and pathological conditions. In recent years, the role of EphA2 in the occurrence and development of cancer has become a research hotspot and is considered a promising potential target. Our previous studies have shown that EphA2 has an indisputable cancer-promoting role in cervical cancer, but its related mechanism requires further research. In this study, high-throughput sequencing was performed on EphA2 knockdown cervical cancer cells and the control group. An analysis of differentially expressed genes revealed that EphA2 may exert its cancer-promoting effect through C-X-C motif chemokine ligand 11 (CXCL11). In addition, we found that EphA2 could further regulate programmed cell death ligand 1 (PD-L1) through CXCL11. This has also been further demonstrated in in vivo experiments. Our study demonstrated that EphA2 plays a tumor-promoting role in cervical carcinoma through the CXCL11/PD-L1 pathway, providing new guidance for the targeted therapy and combination therapy of cervical carcinoma.

Tunable fluorescent amino-functionalized Ti3C2Tx MXene quantum dots for ultrasensitive Fe3+ ion sensing.

The development of sensors with high sensitivity, good selectivity and reproducibility are of great importance for the detection of Fe3+ in contaminated water for environmental monitoring. In this work, a reflux approach has been adopted to synthesize Ti3C2Tx quantum dots (QDs) based on the cutting effect of tetramethylammonium hydroxide (TMAOH) on Ti3C2Tx at high temperature. The surface-functionalized Ti3C2Tx QDs contained abundant amino groups and exhibited tunable pH-dependent emission, which was attributed to the protonation and deprotonation of the surface terminations. The linearity of the radiometric fluorescence intensity versus pH indicates its great potential as a dual-emission ratiometric pH sensor. Additionally, the Ti3C2Tx QDs exhibited tunable excitation-dependent emission behavior, which was related to the degree of passivation by the amino groups on the surface. Furthermore, the fluorescence intensity of the Ti3C2Tx QDs shows a linear response toward Fe3+ in the nanomolar to micromolar range with a low detection limit of 2 nM, originating from the oxidation and reduction between Fe3+ and Ti3C2Tx. This ultra-sensitive and selective detection capability demonstrated the environmental application potential for Ti3C2Tx QDs as a nanoprobe to monitor Fe3+.

LINC01234 regulates microRNA-27b-5p to induce the migration, invasion and self-renewal of ovarian cancer stem cells through targeting SIRT5.

LINC01234 has been suggested to correlate with the survival of ovarian cancer (OS), but its role in the properties of OC stem cells (OCSCs) has been rarely described. We aim to investigate the effect of LINC01234 on the differentiation and self-renewal of OCSCs through adsorption of microRNA (miR)-27b-5p to target sirtuins 5 (SIRT5). Expression of LINC01234 and SIRT5 in OC and normal samples included in TCGA and GTEx was searched through the GEPIA2 database. Bioinformatics analysis was conducted to predict the relation of LINC01234, miR-27b-5p and SIRT5. Expression of LINC01234, miR-27b-5p and SIRT5 in OC tissues and cells was detected. OCSCs were cultured and identified. CD133+ OCSCs were introduced with related oligonucleotides or vectors of LINC01234 or miR-27b-5p and SIRT5 to figure out their roles in OCSCs progression and tumorigenesis in vivo. The interaction of miR-27b-5p with LINC01234 or SIRT5 was analyzed. Bioinformatics analysis suggested that LINC01234 was very likely to influence SIRT5 and regulate the development of OC through miR-27b-5p. Up-regulated LINC01234 exhibited in OC tissues and cells. Down-regulated LINC01234 or elevated miR-27b-5p suppressed OCSCs progression and tumorigenesis in vivo. LINC01234 could restore SIRT5 expression by binding to miR-27b-5p. Down-regulated miR-27b-5p reversed the effect of silenced LINC01234 on OCSCs development and tumorigenesis in vivo. Up-regulation of SIRT5 reduced the effects of elevated miR-27b-5p on OCSCs progression and tumorigenesis in vivo. LINC01234 regulates miR-27b-5p to induce the migration, invasion and self-renewal of OCSCs through targeting SIRT5.

Identification and validation of the high expression of pseudogene TCAM1P in cervical cancer via integrated bioinformatics analysis.

BACKGROUND: HPV as the main cause of cervical cancer has long been revealed, but the detailed mechanism has not yet been elucidated. The role of testis/cancer antigen in cervical cancer has been revealed. However, there are no reports about the statement of testis/cancer-specific non-coding RNA. In this study, we first proposed TCAM1P as a testis/cancer-specific pseudogene, and used a series of experimental data to verify its relationship with HPV, and analyzed its diagnosis value of high-grade cervical lesions and the mechanism of their high expression in cervical cancer. This provides a new direction for the prevention and treatment of cervical cancer. METHODS: The specific expression of pseudogenes in each tissue was calculated by "TAU" formula. ROC curve was used to judge the diagnosed value of TCAM1P for high-grade lesions. The proliferation ability of cells was measured by CCK8. The expression of TCAM1P, HPV E6/E7 were detected by qRT-PCR. The binding for RBPs on TCAM1P was predicted by starbase v2.0 database, then RIP assay was used to verify. Besides, Gene Ontology (GO) and KEGG enrichment analysis were performed with "clusterprofiler" R package. RESULTS: TCAM1P was specifically high-expressed in normal testicular tissue and cervical cancer. Interesting, with the severity of cervical lesions increased, the expression of TCAM1P increased, and TCAM1P could effectively diagnose high-grade cervical lesions. Besides, the expression of TCAM1P was HPV dependent, with highest expression in HPV-positive cervical cancer tissues. Furthermore, RIP assay showed that EIF4A3 regulated the expression of TCAM1P through binding with it. CCK8 assay showed that TCAM1P promoted the proliferation and the Gene ontology (GO) and KEGG Pathway enrichment analysis same suggested that TCAM1P is involved in multiple ways in cell proliferation including Cell cycle, DNA replication and etc. CONCLUSIONS: In this study, we firstly proposed that TCAM1P is cancer/testis pseudogene and is regulated by HPV E6/E7 and EIF4A3. TCAM1P promotes the proliferation of cervical cancer cells and acts as promoter in cervical cancer. Otherwise, TCAM1P promote proliferation through regulating cell cycle and DNA replication, but more evidence needs to be provided to reveal the mechanism by which TCAM1P plays a role in cervical cancer.

A Risk Score Model Incorporating Three m6A RNA Methylation Regulators and a Related Network of miRNAs-m6A Regulators-m6A Target Genes to Predict the Prognosis of Patients With Ovarian Cancer.

Ovarian cancer (OC) is the leading cause of cancer-related death among all gynecological tumors. N6-methyladenosine (m6A)-related regulators play essential roles in various tumors, including OC. However, the expression of m6A RNA methylation regulators and the related regulatory network in OC and their correlations with prognosis remain largely unknown. In the current study, we obtained the genome datasets of OC from GDC and GTEx database and analyzed the mRNA levels of 21 key m6A regulators in OC and normal human ovarian tissues. The expression levels of 7 m6A regulators were lower in both the OC tissues and the high-stage group. Notably, the 5-year survival rate of patients with OC presenting low VIRMA expression or high HNRNPA2B1 expression was higher than that of the controls. Next, a risk score model based on the three selected m6A regulators (VIRMA, IGF2BP1, and HNRNPA2B1) was built by performing a LASSO regression analysis, and the moderate accuracy of the risk score model to predict the prognosis of patients with OC was examined by performing ROC curve, nomogram, and univariate and multivariate Cox regression analyses. In addition, a regulatory network of miRNAs-m6A regulators-m6A target genes, including 2 miRNAs, 3 m6A regulators, and 47 mRNAs, was constructed, and one of the pathways, namely, miR-196b-5p-IGF2BP1-PTEN, was initially validated based on bioinformatic analysis and assay verification. These results demonstrated that the risk score model composed of three m6A RNA methylation regulators and the related network of miRNAs-m6A regulators-m6A target genes is valuable for predicting the prognosis of patients with OC, and these molecules may serve as potential biomarkers or therapeutic targets in the future.

Fatty Acid-Binding Protein 4 (FABP4) Suppresses Proliferation and Migration of Endometrial Cancer Cells via PI3K/Akt Pathway.

PURPOSE: Endometrial cancer (EC) is the sixth most common cancer in women and its incidence and mortality have been rising over the last decades. The latest research indicates that FABP4 plays a significant role in multiple types of cancer. But few studies were focused on EC. The aim of this article is to investigate whether FABP4 can suppress tumor growth and metastasis of EC via PI3K/Akt pathway to provide a novel therapeutic target for the treatment of EC. MATERIALS AND METHODS: FABP4 mRNA levels of EC were analysed through The Cancer Genome Atlas database (TCGA), and expression of FABP4 in EC cancer tissues was determined by immunohistochemistry (IHC) assays. Stable overexpressing cell lines were established using lentivirus infection to analyze the biological function of FABP4 in vitro. CCK8 assay and colony formation assay were performed to assess cell proliferation ability. Wound healing assay and transwell were performed to analyse migration and invasion of cells. The subcutaneous xenograft mouse model was used to evaluate tumor growth in vivo. Additionally, all protein levels were detected by Western blotting assay. RESULTS: We found that the expression of the FABP4 mRNA was decreased in tumor samples compared to normal tissue according to TCGA database analysis. Subsequent experimental mRNA and protein expression analysis confirmed that FABP4 expression was lower in EC tissue than normal endometrial tissue. In addition, we found overexpression of FABP4 inhibited the proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Further functional and mechanistic analysis of FABP4 demonstrated that its function is mediated by restraining the phosphorylation of PI3K/Akt signaling pathway. CONCLUSION: Our studies shed light for the first time about the functional role of FABP4 in EC and provide a novel biomarker for EC as well as a therapeutic target for the therapy of EC.

Semiconducting Nanoparticles: Single Entity Electrochemistry and Photoelectrochemistry.

Semiconducting nanoparticles (SC NPs) play vital roles in several emerging technological applications including optoelectronic devices, sensors and catalysts. Recent research focusing on the single entity electrochemistry and photoelectrochemistry of SC NPs is a fascinating field which has attained an increasing interest in recent years. The nano-impact method provides a new avenue of studying electron transfer processes at single particle level and enables the discoveries of intrinsic (photo) electrochemical activities of the SC NPs. Herein, we review the recent research work on the electrochemistry and photoelectrochemistry of single SC NPs via the nano-impact technique. The redox reactions and electrocatalysis of single metal oxide semiconductor (MOS) NPs and chalcogenide quantum dots (QDs) are first discussed. The photoelectrochemistry of single SC NPs such as TiO2 and ZnO NPs is then summarized. The key findings and challenges under each topic are highlighted and our perspectives on future research directions are provided.

The LINC00922 aggravates ovarian cancer progression via sponging miR-361-3p.

BACKGROUND: Long noncoding RNA (lncRNA) LINC00922 has been reported to promote tumorigenesis of lung and breast cancer. However, the functions and mechanisms of LINC00922 in ovarian cancer (OC) remain unclarified. The current study aims to clarify the detailed functions and underlying mechanisms of LINC00922 in the progression of OC. METHODS: LINC00922 expression in OC tissues and cells was identified by a comprehensive strategy of data miming, computational biology and quantitative real-time polymerase chain reaction (RT-qPCR) experiment. In vitro CCK-8, wound healing, transwell invasion, western blotting and in vivo tumorigenesis assays LINC00922 were conducted to evaluate the functions of LINC00992. Subsequently, bioinformatics technology and dual luciferase reporter assay were performed to confirm the between miR-361-3p and LINC00922 or CLDN1. Finally, rescue experiments were performed to confirm whether LINC00922 effect functions of OC cells through regulation of miR-361-3p. RESULTS: LINC00922 was significantly upregulated in OC tissues and cell lines, which is significantly positively corelated with the poor prognosis of patients with OC. LINC00922 knockdown inhibited proliferation and tumorigenesis of OC cells in vitro and vivo. In addition, LINC00922 knockdown suppressed migration, invasion, and EMT of OC cells in vitro. Mechanically, LINC00922 could competitively bind with miR-361-3p to relieve the repressive effect of miR-361-3p on its target gene CLDN1 in OC cells. In addition, silencing miR-361-3p promoted OC cell proliferation, migration, invasion, EMT and Wnt/ß-catenin signaling, while LINC00922 knockdown inhibited Wnt/ß-catenin signaling by upregulating miR-361-3p. Rescue experiments revealed that LINC00922 knockdown inhibited OC cell proliferation, migration, invasion and EMT by regulating miR-361-3p. CONCLUSION: This study suggested that LINC00922 could competitively bind with miR-361-3p to promote the CLDN1 expression and activate Wnt/ß-catenin signaling in OC progression, which providing a promising therapeutically target for OC.

OSU-03012 Disrupts Akt Signaling and Prevents Endometrial Carcinoma Progression in vitro and in vivo.

PURPOSE: OSU-03012 is a celecoxib derivative lacking cyclooxygenase-2 inhibitory activity and a potent PDK1 inhibitor which has been shown to inhibit tumor growth in various ways. However, the role of OSU-03012 in endometrial carcinoma (EC) in which the PI3K/Akt signaling pathway highly activated has not been studied. Here, we determined the potency of OSU-03012 in suppressing EC progression in vitro and in vivo, and studied the underlined mechanisms. METHODS: The human EC Ishikawa and HEC-1A cells were used as the in vitro models. CCK8 assay and flow cytometry were conducted to evaluate cell proliferation, cell cycle progression, and apoptosis. The metastatic ability was evaluated using the transwell migration assay. The Ishikawa xenograft tumor model was used to study the inhibitory effects of OSU-03012 on EC growth in vivo. Western blot analysis was performed to evaluate expressions of the cell cycle and apoptosis associated proteins. RESULTS: OSU-03012 could inhibit the progression of EC both in vitro and in vivo by disrupting Akt signaling. It reduced the metastatic ability of EC, led to G2/M cell cycle arrest and induced apoptosis via the mitochondrial apoptosis pathway. CONCLUSION: Our data indicated that OSU-03012 could inhibit the progression of EC in vitro and in vivo. It can potentially be used as the targeted drug for the treatment of EC by inhibiting Akt signaling.

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.

Silencing of circular RNA_0000326 inhibits cervical cancer cell proliferation, migration and invasion by boosting microRNA-338-3p-dependent down-regulation of CDK4.

Cervical cancer is one of the leading causes of cancer-related death among women, which is attributed partly by limited treatment options. Recent studies have provided in-depth explanations regarding the role of circular RNA in cancers. We aimed to investigate the role of circular RNA_0000326 in cervical cancer. Bioinformatics analysis revealed a high circ_0000326 expression in cervical cancer. Cervical cancer cells and tissues were also observed to have elevated levels of circ_0000326 and the upregulation of circ_0000326 depended on the stage of cancer. Transfection with siRNA of circ_0000326 resulted in the inhibition of proliferation, migration and cell cycle of cancer cells. Interestingly, we confirmed that circ_0000326 served as a sponge for microRNA-338-3p and that the miRNA bound to Cyclin-dependent kinase 4. In the presence of microRNA-338-3p mimic or silencing of circ_0000326, Cyclin-dependent kinase 4 expression was decreased. Transfection with microRNA-338-3p mimic inhibited cell clone formation and proliferation. Moreover, in vivo experiment revealed that the injection of shRNA-circ_0000326 lentivirus suppressed tumor growth and decreased Cyclin-dependent kinase 4 expression. Taken altogether, our results showed that circ_0000326 exerted oncogenic effects on cervical cancer by upregulating Cyclin-dependent kinase 4 via sponging microRNA-338-3p. This systematic investigation on circ_0000326 could provide further insight into cervical cancer.

Effect of eukaryotic translation initiation factor 4A3 in malignant tumors.

Eukaryotic translation initiation factor 4A3 (EIF4A3), a key component of the exon junction complex, is widely involved in RNA splicing and nonsense-mediated mRNA decay. EIF4A3 has also been reported to be involved in cell cycle regulation and apoptosis. Thus, EIF4A3 may serve as a pivotal regulatory factor involved in the occurrence and development of multiple diseases. Previous studies have demonstrated that EIF4A3 is mutated in neuromuscular degenerative lesions and is differentially expressed in several tumors, serving as a non-coding RNA binding protein to regulate its expression. In addition, studies have reported that inhibiting EIF4A3 can prevent tumor cell proliferation, thus, several researchers are trying to design and synthesize potent and selective EIF4A3 inhibitors. The present review summarizes the function of EIF4A3 in cell cycle and discusses it underlying molecular mechanisms that contribute to the occurrence of malignant diseases. In addition, EIF4A3 selective inhibitors, and bioinformatics analyses performed to analyze the expression and mutations of EIF4A3 in gynecological tumors and breast cancer, are also discussed.

EphA2 promotes tumorigenicity of cervical cancer by up-regulating CDK6.

Erythropoietin-producing hepatocellular receptor A2 (EphA2) receptor tyrosine kinase plays an important role in tissue organization and homeostasis in normal organs. EphA2 is overexpressed in a variety of types of solid tumours with oncogenic functions. However, the role of EphA2 in cervical cancer (CC) is still needed to be further explored. Here, we examined the role of EphA2 by establishing a stable EphA2 knock-down CC cell lines or a stable EphA2-overexpressed CC cells lines. Overexpression of EphA2 increased cell proliferation and migration of CC while EphA2 knock-down decreased the CC tumorigenicity. In addition, EphA2 knock-down suppressed CC tumour development in the xenograft mouse model. Inhibition of EphA2 by AWL-II-41-27, EphA2-specific tyrosine kinase inhibitor, or knock-down of EphA2 decreased mRNA and protein expression of cyclin-dependent kinase (CDK) 6 in CC cells, which increased cellular susceptibility to epirubicin (EPI), an anti-cancer chemotherapy drug. A clinicopathological study of EphA2 was conducted on a cohort of 158 human CC patients. EphA2 protein expression was positively correlated with CDK6 protein expression, invasion depth, lymph node metastasis and clinicopathological stage (P < .05). This study demonstrates the oncogenic activity of EphA2 in vitro and in vivo, which provides insights into the relevant mechanisms that might lead to novel treatments for CC.

Characterization of Kinesin Family Member 2C as a Proto-Oncogene in Cervical Cancer.

Kinesin family member 2C (KIF2C) is known as an oncogenic gene to regulate tumor progression and metastasis. However, its pan-cancer analysis has not been reported. In this study, we comprehensively analyzed the characteristics of KIF2C in various cancers. We found that KIF2C was highly expressed and corresponded to a poor prognosis in various cancers. We also found a significant correlation between KIF2C and clinicopathological characteristics, particularly in cervical cancer, which is the most common gynecological malignancy and is the second leading cause of cancer-related deaths among women worldwide. KIF2C mutation is strongly associated with the survival rate of cervical cancer, and KIF2C expression was significantly upregulated in cervical cancer tissues and cervical cancer cells. Moreover, KIF2C promoted cervical cancer cells proliferation, invasion, and migration in vitro and as well increased tumor growth in vivo. KIF2C knockdown promotes the activation of the p53 signaling pathway by regulating the expression of related proteins. The rescue assay with KIF2C and p53 double knockdown partially reversed the inhibitory influence of KIF2C silencing on cervical cancer processes. In summary, our study provided a relatively comprehensive description of KIF2C as an oncogenic gene and suggested KIF2C as a therapeutic target for cervical cancer.

miR-96 enhances the proliferation of cervical cancer cells by targeting FOXO1.

MiRNAs affect various biological pathways associated with the development, progression, clinical outcome and treatment response improvement in cervical cancer. This study was performed to evaluate the effects of miRNA 96 on cervical cancer and to clarify the mechanism. Vivo and vitro experiments were conducted in our trial. MiR-96 is upregulated in cervical cancer cell lines and cervical cancer tissues and is correlated with clinical features in cervical cancer patients. Overexpression of miR-96 enhances proliferation of cervical cancer cells, while inhibiting miR-96 reduces the proliferation of cervical cancer cells. Inhibition of miR-96 significantly decreased the percentage of cells in the S phase and increased the percentage of cells in G1/G0 peak in both SiHa and CaSki cells compared with NC cells and decreased the expressions of p21, p27 and cyclin D1. FOXO1 3'-UTR was sub cloned into a luciferase reporter vector and the putative miR-96 binding site in the FOXO1 3'-UTR was mutated. Treated with miR-96 inhibitor consistently enhanced the luciferase activity of the FOXO1 3'-UTR luciferase reporter plasmids in both SiHa and CaSki cells, whereas mutations in the miR-96-binding site abolished the effect. Vivo experiment also support these results. Therefore, inhibition of miR-96 might suppress growth, proliferation of CC cells and promote apoptosis of CC cells both in vitro and in vivo.