Cervical cancer poses a serious threat to women's health. Emerging evidence indicates that changes in the cervicovaginal microbiota (CVM) and vaginal microenvironment may play a crucial role in cervical carcinogenesis. In this study, we examined CVM and vaginal microenvironment profiles in 510 participants with varying stages of cervical lesions using 16S rRNA sequencing, vaginal pH and H2O2 measurements, and cleanness assessment. A co-occurrence network and generalized multifactor dimensionality reduction model were employed to analyze the correlation and interaction between microbial taxa and microenvironment profile. Our results demonstrated that CVM disorder and abnormal vaginal microenvironment were associated with cervical lesions. As cervical cancerization progressed, the abundance of Lactobacillus gradually decreased with thriving anaerobe levels in the deteriorating vaginal microenvironment. This interaction was characterized by high vaginal pH, a non-Lactobacillus-dominant microbiota, and high CVM diversity (Shannon index ≥ 0.81). Co-occurrence network analysis revealed that abnormal pH and H2O2 levels correlated with Lactobacillus depletion and had a positively co-occurring relationship with anaerobes in precancerous cervical lesions. CVM function significantly varied with changes in the vaginal microenvironment across different stages of cervical lesions. Our findings suggest that CVM dysbiosis, particularly when combined with an abnormal vaginal microenvironment, may promote the progression of cervical lesions. This highlights the importance of addressing vaginal microecology to prevent cervical carcinogenesis.IMPORTANCECervicovaginal microbiota (CVM) and vaginal microenvironment in human papillomavirus infection are associated with the progression of cervical carcinogenesis. CVM dysbiosis, particularly the decrease in Lactobacillus and the increase in anaerobes, is crucial in promoting the malignant progression of cervical lesions. As cervical carcinogenesis progresses, the relative abundance of anaerobes increases in the deteriorating vaginal microenvironment. We systematically analyzed the relationship between CVM and the vaginal microenvironment in cervical lesions, aiming to reveal the contribution of CVM with specific vaginal microenvironmental features and its functional changes in the progression of cervical carcinogenesis. Our results may provide new insights into the etiology and pathogenesis of cervical cancer from the perspective of vaginal microecology.

Unlike the well-studied cervical cancer caused by human papillomavirus (HPV), there is a lack of epidemiological data on HPV, which covers the entire lower genital tract and has regional characteristics. This study investigated the HPV distribution in cervical, vaginal and vulvar lesions to provide a reference for their integrated management. This cross-sectional study was designed using the data from the Second Hospital of Shanxi Medical University between January 2014 and December 2023. Study participants underwent colposcopy and targeted biopsy. Pathological diagnosis of cervical, vaginal and vulvar lesions were performed. Participants were divided into different groups according to pathological diagnosis. The clinical characteristics and HPV infection status were analyzed. The attributable risk percentage (AR

OBJECTIVE:Vaginal cancer is a rare malignancy, and the research on it is not comprehensive yet. To explore the characteristics of human papillomavirus (HPV) infection in patients with vaginal intraepithelial neoplasia (VaIN) and vaginal cancer. MATERIALS AND METHODS:This study included patients who underwent colposcopy and biopsy of suspected sites at the Second Hospital of Shanxi Medical University from January 2014 to December 2023 due to abnormal cytology results and/or positive HPV test. Those diagnosed with benign inflammatory reaction of the vagina (ie, vaginitis), VaIN and vaginal cancer according to histologic results were selected as the study objects. Clinical data such as age, menopause, clinical manifestations and previous screening history were collected. We aimed to analyze the distribution and characteristics of HPV in VaIN and vaginal cancer patients. RESULTS:A total of 5,180 patients were included in this study. Of the total, 2,739 patients had VaIN1, 641 had VaIN2/3, and 251 had vaginal cancer. There were 235 patients with vaginal squamous cell carcinoma (VaSCC) and 16 patients with vaginal adenocarcinoma. A total of 4,548 patients were infected with HPV. The HPV positive rate was 95.5% in VaIN2/3, 86.0% in VaSCC and 43.8% in adenocarcinoma of the vagina. The most common 5 HPV types were HPV16, 52, 58, 53, and 18. The positive rate of HPV18 in the adenocarcinoma of the vagina was the highest. CONCLUSION:HPV16, 52, 58, 53, and 18 are the predominant genotypes in VaIN and vaginal cancer in Shanxi, China. HPV testing provides additional benefits for the detection of vaginal lesions during cervical cancer screening. Active HPV vaccination may help reduce the burden of these lesions.

Cervical cancer poses a significant threat to women’s health. Although folic acid (FA) has been recognized as a protective factor in cervical carcinogenesis, its precise molecular mechanisms remain incompletely understood. Here, we identify Dickkopf Wnt signaling pathway inhibitor 3 (DKK3), an inhibitor of the Wnt signaling pathway, as a potential target of FA. This study provides systematic evidence that DKK3 expression decreases during cervical squamous epithelial carcinogenesis, showing progressive downregulation from squamous intraepithelial lesions to squamous cell carcinoma, which correlates with advanced FIGO stage and lymphovascular space invasion. Functional assays confirmed DKK3’s tumor-suppressive role and therapeutic potential. DKK3 overexpression downregulated β-catenin protein levels and inhibited malignant behavior in SiHa cells, whereas its knockdown produced opposite effects. Notably, this study demonstrated for the first time that FA intervention upregulated DKK3 expression, suppressed Wnt/β-catenin signaling, leading to a reduction in β-catenin protein abundance, and exerted potent anti-tumor effects—suppressing proliferation, migration, and invasion while promoting apoptosis. Even under DKK3-knockdown conditions, FA intervention partially reversed β-catenin accumulation by enhancing residual DKK3 expression. Overall, this study establishes the prognostic and interventional value of DKK3 in cervical squamous epithelial carcinogenesis. FA intervention may serve as an effective strategy to restore DKK3 expression to inhibit the Wnt/β-catenin pathway, thereby exerting antitumor activity. Future cervical cancer prevention and treatment strategies may benefit from dynamic monitoring of DKK3 expression to identify potential beneficiaries and provide targeted FA intervention.

Background:Cluster of Differentiation-4(CD4),Cluster of Differentiation-8(CD8), and interleukin-10 (IL-10) have long been considered to be related to cervical cancer, but the exact relationship remains unclear. Few studies investigated the relationship between CD4,CD8,IL-10, and high-risk human papillomavirus (HPV) with risk of cervical intraepithelial neoplasia (CIN). Objective:Our aim is to evaluate the relationship between CD4, CD8, IL-10, and high-risk HPV infection with the risk of CIN, as well as their interactions on CIN. Design:In 2014-2015, a cross-sectional study of screening data was conducted among 2285 women aged 19-65 years who participated in an ongoing community-based cohort of 40,000 women in Shanxi, China. Using categorical and spline analyses to evaluate the relationship between local vaginal fluids of CD4,CD8,CD4/CD8,IL-10, and CIN risk. A total of 1,503 controls were followed up until January 31, 2019. A nested case-control study was used to assess the relationship between vaginal lavage CD4, CD8, CD4/CD8, and IL-10 levels and the risk of CIN progression. Results:After adjusting for possible confounding factors,CD4 and CD8 levels were positively related to CIN risk (the 1st versus 4th quartile CD4,CD8 OR = 0.45[0.34, 0.60] and 0.34[0.26, 0.45] for CIN1, 0.32 [0.21, 0.48] and 0.24 [0.16, 0.38] for CIN2/3). Increased CD4 and CD8 levels were positively related to the occurrence of CIN(P-overall<0.01).CD4/CD8 levels and the risk of CIN1 followed a nonlinear "U-shape" (P-nonlinear <0.01). IL-10 levels and the risk of CIN1 followed a nonlinear "n-shape"(P-nonlinear <0.01).IL-10 levels were inversely related to the occurrence of CIN2/3(OR = 3.87, [2.49, 6.00],P-overall<0.01). The highest risk of CIN was observed in women with high-risk HPV, whose CD4 and CD8 levels were the highest(P-interaction < 0.01).Patients with the lowest IL-10 levels(IL-10 ≤ 53.17pg/ml) who are positive for high-risk HPV infection have the highest risk of CIN2/3(OR = 18.46,[9.33-36.51]). Nested case-control analysis observed a positive relationship between CD4,CD8 levels, and risk of CIN progression (CD4 OR = 0.34,[0.13, 0.94];CD8 OR = 0.27, [0.09, 0.79]),and an opposite relationship between IL-10 levels and risk of CIN progression (OR = 2.92, [1.09, 7.84]). Conclusions:Local vaginal CD4 and CD8 levels were positively correlated with CIN risk, and IL-10 levels were inversely correlated with CIN2/3, whether or not with high-risk HPV infection in Chinese women.

Ovarian cancer (OC) is the leading cause of death from gynecological malignancies worldwide. Alterations in mitochondrial metabolism are considered defining characteristics and therapeutic targets of OC. Olaparib, an oral inhibitor of poly (ADP-ribose) polymerase, has been approved for the treatment of OC. However, the precise mechanisms by which it exerts its effects remain unclear. In this study, we uncover a novel pharmacological function of Olaparib by demonstrating that it induces mitochondrial dysfunction in human SKOV3 ovarian cancer cells. Our findings revealed that Olaparib exposure induced mitochondrial oxidative stress by elevating mitochondrial ROS levels and diminishing GPx activity. Additionally, treatment with Olaparib led to mitochondrial dysfunction, as evidenced by decreased complex I and complex IV activity and reduced ATP production. We observed that Olaparib induced mitochondrial fission by decreasing the average length of mitochondria. Olaparib did not affect the levels of Mfn1, Mfn2, or the total expression of Drp-1. Intriguingly, Olaparib increased the levels of phosphorylated Drp-1 at Ser616. Further investigation revealed that Olaparib facilitated the activation of the CDK5 signaling pathway and induced Caspase 3 activation. Notably, inhibition of CDK5 signaling using roscovitine mitigated the effects of Olaparib on mitochondrial fission and dysfunction, indicating a role for CDK5 in this process. In summary, our research identifies that CDK5/Drp-1-mediated mitochondrial fission may represent a novel mechanism through which Olaparib exerts its anticancer effects in OC.

OBJECTIVE:To evaluate detection rates of multisite lesions (cervical, vaginal, vulvar) among women attending colposcopy clinics. METHODS:Our cross-sectional study included 20,486 patients between 2014 and 2023 in Shanxi China. Detection rates for cervical, vaginal, and vulvar lesions were retrospectively analyzed across strata by HPV status, cytological diagnosis, and clinical manifestations (vaginal bleeding/discharge). Multinomial logistic regression was applied to calculate odds ratios for high-grade lesions and squamous cell carcinoma (SCC). RESULTS:High-risk HPV (hr-HPV) infection was detected in 16,636 of 20,486 women (81.2%), and 9,137 (44.6%) had ASC-US+ cytology. Following cervical lesion detection on histopathology among hr-HPV-positive women (CIN2/3: 19.9%; SCC: 5.3%; AIS/ADC: 0.4%), additional lesions were identified at other anatomical sites: vaginal lesions (VaIN2/3: 3.6%; SCC: 1.1%; AIS/ADC: 0.04%) and vulvar lesions (VIN2/3: 0.4%; SCC: 0.1%) were further identified. Overall, 21.6% of hr-HPV-positive women exhibited high-grade lesions (CIN/VaIN/VIN2/3), with 5.6% demonstrating multi-focal SCC and 0.4% showing AIS/ADC. Stratified analysis revealed that patients even with negative HPV or cytology result still had relative high detection rate of high-grade lesions. Among these HPV-negative women, those reporting vaginal bleeding/discharge carried an elevated risk, with 3.2% having high-grade lesions and 10.5% having SCC. The integrative examination combining hr-HPV, cytology, and vaginal bleeding/discharge identified 3,753 high-grade lesions and 1,154 cancers. CONCLUSION:Integrating the assessment of hr-HPV testing, cytology, and clinical symptoms (e.g., vaginal bleeding or discharge) could help finding more cases of multisite lesions (cervical, vaginal, vulvar). This is especially important for some high-risk women, including those who visit the colposcopy clinics, and more attention should be paid to the multisite examination.

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia.

IntroductionThe etiology and clinical presentation of vulvar carcinomas, especially vulvar lesions, are not fully understood. Because the vulva and cervix are anatomically connected, human papillomavirus (HPV) is the main cause of cervical lesions. Thus, this study explored the potential characteristics and effects of specific HPV infection types across vulvar lesions and concurrent cervical lesions.MethodsThis retrospective, cross-sectional study analyzed patients with cervical HPV or cytological results and concurrent vulvar biopsy who were seen in our hospital colposcopy clinic in Shanxi Province, China, between 2013 and 2023. Data on age, menopause status, vulvar manifestations, and cytology and HPV infection testing results were collected. Attributable fractions and multinominal logistic models were used to evaluate HPV genotyping and clinical characteristics across vulvar lesions.ResultsAmong the 1,027 participants, 83 (8.1%) had vulvar intraepithelial neoplasia (VIN) of high grade or worse (VIN2+), and 127 (12.4%) had non-neoplastic epithelial disorders of the vulva (NNEDV). A total of 175 patients had either VIN2+ or cervical intraepithelial neoplasia (CIN) lesions of grade 2 or worse (CIN2+). The most common HPV genotypes for VIN2+ or concurrent VIN2+/CIN2+ were HPV16, HPV52, and HPV58, although attributable fractions differed among lesions. Patients with normal cytological or histopathological result were more likely to have NNEDV detected, while abnormal cervical diagnosis was associated with higher detection of VIN2+. Multinominal logistic modeling showed that age and HPV16 infection were risk factors for VIN2+ or concurrent VIN2+/CIN2+; however, only vulvar presentation with depigmentation was a risk factor for NNEDV. Among patients with low-grade CIN1/VIN1, compared with those who were HPV16 negative, those who were HPV16 positive were at 6.63-fold higher risk of VIN2+/CIN2+ [95% confidence interval (CI): 3.32, 13.21]. Vulvar depigmentation was also associated with increased risk of NNEDV (odds ratio: 9.98; 95% CI: 3.02, 33.04).ConclusionsChinese women may be at specific, high risk for HPV infection types associated with VIN or CIN. The use of cervical cell HPV detection along with vulvar presentation during cervical cancer screening may also contribute to vulvar lesion detection.

Objective To explore the characteristics of vaginal microbiota in women with abnormal cervical cytology under different HPV16 infection status, and to predict the function of the vaginal microbiota. Methods A total of 132 women with abnormal cervical cytology by liquid-based thinprep cytologic test（TCT）, who came from the gynecological clinic of Second Hospital of Shanxi Medical University during January to June 2018, were enrolled in this study. Flow-through Hybridization technology was used to determine HPV infection typing. The vaginal microbiota was detected by 16S rDNA sequencing. The characteristic of vaginal microbiota were described by bio informatics, and Kyoto Encyclopedia of Genes and Genomes（KEGG） database was used to analyze the function of the vaginal microbiota. Results The Simpson index in the HPV16 positive group（n=59） was lower than that in the negative（n=73） group（P=0.047）, while the Shannon index was higher in the positive group（P=0.036）. Non-metric multidimensional scaling（NMDS） based on Bray-Curtis dissimilarities showed that there was no significance in Beta diversity between the two groups（P=0.199）. Lactobacillus was the dominant bacteria in women with abnormal cervical cytology and different HPV16 infection status, but the proportion of Lactobacillus decreased（57.50%vs.60.69%） and anaerobic bacteria such as Gardnerella（14.29%vs.13.66%）, and Peptoniphilus（4.28%vs.2.99%） increased in the HPV16 positive group. The abundance of Lactobacillus, Enterococcus, Staphylococcus and so on in the negative group was higher than that in the positive group, while the abundance of anaerobic bacteria such as Gardnerella, Ureaplasma, Peptoniphilus, Prevotella and so on in the HPV16 positive group was higher than that in the negative group. Ureaplasma and Peptoniphilus were the characteristic bacteria in HPV16 positive women based on Linear discriminant analysis Effect Size（LEfSe） analysis. The functional analysis showed that the function of vaginal microbiota was mainly concentrated on metabolism. The vaginal microbiota function in the HPV16 positive group was mainly to destroy the vaginal microenvironment and promote cell carcinogenesis, while the negative group was mainly to metabolism and inhibit cancer. Conclusions Increased diversity and the composition variation of vaginal microbiota are closely related to HPV16 infection. Ureaplasma and Peptoniphilus might be considered as potential biomarkers for HPV16 infection. Vaginal microbiota under HPV16 infection might induce vaginal microenvironment disorder and promote cancer.

自噬在病毒感染的反应中调节细胞命运[1] ,在维持细胞稳态和功能中发挥关键作用[2] . 大量证据表明,自噬不仅对氧化应激、DNA损伤、缺氧、营养缺乏、内质网应激以及外源生物或药物的暴露做出一系列适应性反应,以维持体内平衡,而且还参与了人类疾病的发展,包括癌症、脑卒中、神经退行性疾病等[3-5] .

BackgroundAlthough interleukin-2 (IL-2) has long been associated with cancer development, its roles in the development of cervical cancer remains unclear. Few studies examined the associations between IL-2 and high-risk human papillomavirus (HPV) with risk of cervical intraepithelial neoplasia (CIN).ObjectiveWe aimed to assess the association of IL-2 and high-risk HPV infection with risk of CIN as well as their interactions on the risk of CIN.DesignWe performed a cross-sectional analysis of screening data in 2285 women aged 19-65 years who participated in an ongoing community-based cohort of 40,000 women in Shanxi, China in 2014-2015. Both categorical and spline analyses were used to evaluation the association between IL-2 in the local vaginal fluids and prevalence of CIN. In addition, 1503 controls were followed up until January 31, 2019), the nested case-control study design was adopted to evaluate the association of vaginal lavage IL-2 levels and the risk of CIN progression.ResultsAfter adjusting for potential confounders, IL-2 levels were statistically inversely associated with prevalence of CIN (the 1st versus 4th quartile IL-2 levels: the respective odds ratio [OR] and 95% confidence intervals [CI] was: = 1.75 [1.37, 2.23] for CIN, 1.32 [1.01, 1.73] for CIN I, and 3.53 [2.26, 5.52] for CIN II/III). Increased IL-2 levels were inversely associated with prevalence of CIN (P-overall<0.01, P-nonlinearity<0.01 for CIN; P-overall<0.01, P-nonlinearity = 0.01 for CIN I; P-overall <0.01, P-nonlinearity = 0.62 for CIN II/III). The highest prevalence of CIN was observed in women with high-risk HPV, who also had the lowest IL-2 levels (P-interaction < 0.01). Nested case-control study observed an inverse association between IL-2 levels and risk of CIN progression (OR=3.43, [1.17, 10.03]).ConclusionsIL-2 levels in the local vaginal fluids were inversely associated with the risk of CIN in Chinese women either with or without high-risk HPV infection.

HPV特异性感染人体皮肤及黏膜,是宫颈病变的重要发病因素,随着研究的不断深入,除宫颈外的生殖道皮肤黏膜病变逐渐被重视,研究表明,HPV不仅在宫颈病变的发生、发展过程中起重要作用,在外阴病变中也有一定的作用.HPV感染可能与外阴硬化性苔藓、外阴单纯性苔藓、外阴上皮内瘤变及外阴癌相关,参与外阴病变的发生及恶性进展,并影响外阴病变的预后.

Calcium binding and coiled-coil domain 1 (CALCOCO1) is an autophagy regulatory protein being discovered in recent years, which plays an important role in selective autophagy process. The gene coding for autophagy is located at 12q13.13, and its coding protein is CALCOCO1 protein. Which functions by binding to ATG8 family proteins, it anchors to the endoplasmic reticulum and the Golgi apparatus and thus initiate the autophagy of endoplasmic reticulum and Golgi aparatus, and thereby participating in selective autophagy and early stages of autophagosome formation. When the mTOR pathway is activated, mTOR regulates the expression of CALCOCO1 through the autophagy-dependent pathway. CALCOCO1 plays a role in the occurrence and metastasis, and so is a potential target for chemotherapy of malignant tumors.

几乎90％以上的宫颈癌都有高危人乳头瘤病毒(high risk human papilloma virus,HR-HPV)的持续感染,尤其当患者感染HPV16时,高级别宫颈上皮内瘤变或宫颈癌的发生风险可进一步上升.研究表明人类肿瘤中存在低氧现象,缺氧诱导因子1α(hypoxia-inducible factor-1α,HIF-1α)与低氧微环境关系最为密切,HIF-1α的活化能促进肿瘤生长,已成为目前的研究热点.经典的磷脂酰肌醇3激酶(phosphoinositide 3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)自噬通路抑制自噬,并且在多种人类肿瘤中表达失调,其异常活化使细胞异常增殖、分化,促进肿瘤生长.综述HPV16感染可能引起HIF-1α与PI3K/Akt自噬通路变化的不同机制,探讨HPV16相关宫颈癌中PI3K/Akt自噬通路及HIF-1α的表达意义.

BACKGROUND:Although folate status is associated with cervical carcinogenesis, it is not clear whether folate deficiency is associated with risk of cervical intraepithelial neoplasia (CIN) progression and infection with high-risk human-papillomavirus (hrHPV).OBJECTIVES:To evaluate the associations of RBC and serum folate concentrations with prevalence of CIN grades and hrHPV infection, their interactions with prevalence of CIN grades, and RBC folate with the risk of CIN1 progressing to CIN2.METHODS:Using data from the Shanxi CIN cohort of 2304 female Chinese adults, we used logistic-regression model to estimate ORs and prevalence ratios (PRs) of RBC and serum folate concentrations with prevalence of CIN grades and hrHPV infection. Categoric and spline analyses were used to evaluate the dose-response relations. We estimated the association of RBC folate with risk of CIN1 progressing to CIN2 in the nested case-control cohort.RESULTS:An inverse association was observed between increased RBC folate concentration and the odds of all CIN grades [quartile 1 (Q1) compared with Q4: OR: 2.28; 95% CI: 1.77, 2.93; Ptrend < 0.001]. Significant interaction of RBC folate and hrHPV infection was observed for prevalence of CIN2 or above (Pinteraction < 0.01). No associations were found between RBC and serum folate with PRs of hrHPV in each CIN grade. Over a median follow-up of 21.0 mo, RBC folate was associated with increased risk of CIN1 progressing to CIN2 (Q1 compared with Q4: OR: 3.86; 95% CI: 1.01, 14.76).CONCLUSIONS:Our study indicates that RBC folate concentration is associated with prevalence of CIN grades and CIN1 progression in female Chinese adults. Maintenance of normal folate status is important for reducing the risk of CIN and its progression in women with or without hrHPV infection.

This study investigated the role of the family with sequence similarity 201-member A (FAM201A), as previously reported oncogenic, in cervical cancer (CC). FAM201A expression in CC was analyzed through bioinformatics analyses, and its distribution in CC tissues/cells was determined by in situ hybridization. CC cells were transfected/cotransfected with FAM201A/flotillin-1 (FLOT1) overexpression plasmids and miR-1271-5p mimics, followed by functional analysis on viability, migration and invasion. Pearson's correlation tests were performed to analyze the correlation between FAM201A and miR-1271-5p in CC tissues. The targeting relationship between miR-1271-5p and FLOT1 was confirmed by dual-luciferase reporter assay. The expressions of FAM201A, miR-1271-5p, FLOT1, matrix metalloproteinases (MMP)-9, MMP-2, E-cadherin, N-cadherin, and the Wnt/β-catenin pathway-related molecules (Wnt1, β-catenin and p-β-catenin) in CC cells or tissues were assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and/or western blot. The results showed that FAM201A was abundantly expressed and miR-1271-5p expression was downregulated in CC. FAM201A was enriched in CC cell cytoplasm and negatively correlated with miR-1271-5p in CC tissues. FAM201A overexpression enhanced the cell viability, migration, invasion, and tumorigenesis of CC in vivo and increased FLOT1 expression. These trends were all reversed by upregulating miR-1271-5p, which induced opposite effects to FAM201A overexpression. MiR-1271-5p upregulation depleted the levels of MMP-9, MMP-2, N-cadherin, and the Wnt/β-catenin pathway-related molecules and upregulated E-cadherin expression. FLOT1 was a direct target of miR-1271-5p. FLOT1 overexpression induced effects contrary to the upregulation of miR-1271-5p and abolished miR-1271-5p upregulation-induced effects in CC cells. Overall, this study showed that FAM201A promoted cervical cancer progression and metastasis by targeting the miR-1271-5p/FLOT1 axis-induced Wnt/β-catenin pathway.

宫颈癌是全世界常见的女性恶性肿瘤.由于肿瘤转移或复发,特别是对于那些晚期肿瘤患者,宫颈癌的总体预后仍然很差.肿瘤转移约占所有与癌症相关死亡的90％.因此,鉴定转移的原因和潜在标志物对于促进早期诊断,预测预后和制定新的宫颈癌治疗策略具有重要意义.在宫颈癌的发展和恶性进展期间,许多microRNA(miRNA)已被证明能显著失调.越来越多的证据表明,miRNA可以有效调节上皮间质转化(EMT)的过程,miRNA包含控制EMT信号通路和直接靶向EMT转录因子进而调节癌细胞的侵袭和转移性,本文将简要阐明miRNA调控EMT对宫颈癌侵袭转移性的影响.

生命早期被认为是肠道微生物区系定植建立的关键时期,早在妊娠期间,母体各部位的微生物便发生了重大变化,并于分娩时传递到新生儿身上[1].接下来随着母乳喂养、年龄增长、饮食逐渐多样化,婴幼儿的肠道微生物区系进一步定植发展,丰富度和多样性不断增加,约在3岁时达到类似于成人的状态[2].近年来的研究发现,这一时期肠道微生物尤其是一些诸如双歧杆菌、类杆菌等特殊菌种的定植决定着短链脂肪酸、维生素、共轭亚油酸等重要代谢物的产生,对个体生长发育、新陈代谢尤其是免疫系统的塑造有着重要意义.