CircUBE2D2 regulates HMGB1 through miR-885-5p to promote ovarian cancer malignancy.

BACKGROUND: The newly discovered CircUBE2D2 has been shown to abnormally upregulate and promote cancer progression in a variety of cancers. The present study explored circUBE2D2 (hsa_circ_0005728) in Ovarian Cancer (OC) progression. METHODS: CircUBE2D2, miR-885-5p, and HMGB1 were examined by RT-qPCR or WB. SKOV-3 cell functions (including cell viability, apoptosis, migration, and invasion) were validated using the CCK-8, flow cytometry, scratch assay, and transwell assay, respectively. The direct relationship between miR-885-5p and circUBE2D2 or HMGB1 was confirmed by a dual-luciferase reporter and RNA pull-down analysis. circUBE2D2's role in vivo tumor xenograft experiment was further probed. RESULTS: OC tissue and cell lines had higher circUBE2D2 and HMGB1 and lower miR-885-5p. Mechanically, CircUBE2D2 shared a binding relation with miR-885-5p, while miR-885-5p can directly target HMGB1. Eliminating circUBE2D2 or miR-885-5p induction inhibited OC cell activities. However, these functions were relieved by down-regulating miR-885-5p or HMGB1 induction. Furthermore, circUBE2D2 knockout reduced tumor growth. CONCLUSION: CircUBE2D2 regulates the expression of HMGB1 by acting as a sponge of ceRNA as miR-885-5p, thereby promoting the control of OC cell proliferation and migration and inhibiting cell apoptosis. Targeting CircUBE2D2 could serve as a new potential treatment strategy for OC.

Aspirin Suppressed PD-L1 Expression through Suppressing KAT5 and Subsequently Inhibited PD-1 and PD-L1 Signaling to Attenuate OC Development.

Ovarian cancer (OC) is a frequently occurred malignancy with high incidence and poor survival worldwide. In recent years, immune checkpoint inhibition that targets PD-1/PD-L1 axis has become an efficient and popular therapy for cancers. Aspirin (ASP), an anti-inflammatory drug, exhibits a wide spectrum of biological functions including anticancer property. However, the role of ASP treatment in ovarian cancer treatment remains unclear. In this work, we explored the role of ASP in modulating PD-L1 signaling during OC development. Notably, in vitro experiments showed that ASP treatment caused repressed proliferation of OC cells. The results from in vivo xenograft model suggested suppressed tumor growth and tumor weight under ASP treatment. ASP treatment also caused downregulated PD-L1 and Ki-67 levels in mice tumors. Moreover, the IFN-γ-caused PD-L1 accumulation was inhibited by ASP treatment. The administration of ASP decreased the expression of PD-L1 of OC cells in a coculture system with activated T cell or unstimulated PBMCs, along with decreased expression of PD-1 by activated T cells. ASP reversed PD-L1 expression caused by coculture with activated T cells and abolished the suppressed T cells activation and proliferation. Analysis on molecular mechanisms revealed that KAT5 bonded to the promoter region of PD-L1 and upregulated its expression via enhancing histone H3 lysine 27 acetylation (H3K27ac), whereas ASP downregulated KAT5 expression and blocked this phenomenon. Moreover, ASP enhanced the effect of antiPD-L1 therapy in the in vivo tumor model. Hence, we proposed that ASP decreased expression of PD-L1 protein via inhibiting the epigenetic regulation by KAT5 and suppressed the PD-1/PD-L1 signaling to attenuate tumor growth. ASP may be a promising adjuvant in OC immunotherapy.

Long Noncoding RNA RMRP Contributes to Paclitaxel Sensitivity of Ovarian Cancer by Regulating miR-580-3p/MICU1 Signaling.

Ovarian cancer is a prevalent female malignancy affecting the health and life of an increasing population of women around the world. Paclitaxel (PTX) resistance is a significant clinical problem in the treatment of ovarian cancer. However, the regulation mechanism of PTX resistance remains unclear. In this investigation, we reported an innovative function of the long noncoding RNA RMRP in promoting PTX resistance and glycolysis of ovarian cancer cells. We observed that RMRP was highly expressed in the ovarian cancer samples, in which the expression of RMRP was elevated in the PTX-resistant patients compared with the PTX-sensitive patients. Meanwhile, RMRP was upregulated in PTX-resistant ovarian cancer cell lines. Functionally, we found that the silencing of RMRP by siRNA significantly enhanced the PTX sensitivity of PTX-resistant ovarian cancer cells, in which the IC50 of PTX was reduced by RMRP depletion. The RMRP knockdown reduced cell viabilities and enhanced cell apoptosis of PTX-resistant ovarian cancer cells. Moreover, we observed that glucose uptake was enhanced in PTX-resistant ovarian cancer cells. The depletion of RMRP decreased glucose uptake, lactate product, and ATP production in PTX-resistant ovarian cancer cells. About the mechanism, we identified that RMRP was able to sponge miR-580-3p to enhance mitochondrial calcium uptake 1 (MICU1) expression in PTX-resistant ovarian cancer cells. MICU1 overexpression and miR-580-3p repression could reverse the RMRP-inhibited proliferation of PTX-resistant ovarian cancer cells in vitro. Thus, we concluded that RMRP contributes to PTX resistance and glycolysis of ovarian cancer by enhancing MICU1 expression through sponging miR-580-3p. Targeting RMRP may serve as a potential therapeutic strategy for the treatment of PTX-resistant ovarian cancer patients.

Comprehensive Analysis Identifies Potential Ferroptosis-Associated mRNA Therapeutic Targets in Ovarian Cancer.

Objective: This study aimed to explore ferroptosis-related mRNAs as potential therapeutic targets for ovarian cancer treatment. Methods: Molecular subtypes were classified based on ferroptosis-related mRNAs via ConsensusClusterPlus package. The differences in prognosis, stromal score, immune score, immune function, and immune checkpoints were assessed between subtypes. Small molecular drugs were predicted via the CMap database. The sensitivity to chemotherapy drugs was estimated through the GDSC. A LASSO Cox regression model was conducted via the glmnet package, followed by a nomogram model. Results: Based on ferroptosis mRNA expression profile, two molecular subtypes (C1 and C2) were classified, with distinct clinical outcomes. C1 subtype exhibited higher stromal score, immune cell score (T helper, Treg, neutrophil) and immune function (APC co-inhibition, parainflammation and Type II IFN response). Higher mRNA expression levels of immune checkpoints (like PDCD1) were found in C1 than C2. Potential small molecular drugs (PI3K and mTOR inhibitors) were found for treatment of ovarian cancer. C1 was more sensitive to eight chemotherapy drugs (A.443654, AZD.0530, AZD6482, AZD7762, AZD8055, BAY.61.3606, Bicalutamide, and CGP.60474). A 15-ferroptosis-related mRNA signature was developed, which could robustly and independently predict the outcomes. Moreover, a nomogram was established combining the signature and age, which could intuitively and accurately predict the 5-year overall survival probability. Conclusion: Our study characterized two ferroptosis-related subtypes with distinct prognosis and tumor immune features, which could assist clinicians make decisions and individual therapy. Moreover, 15 ferroptosis-related mRNAs were identified, which could become potential therapeutic targets for ovarian cancer.

MicroRNA-32 promotes ovarian cancer cell proliferation and motility by targeting SMG1.

Ovarian cancer (OC) is the most lethal gynecological malignancy and one of the leading causes of cancer-related deaths among women. Metastasis is the main cause of poor prognosis in OC. MicroRNA (miRNA/miR) has been shown to play an important role in tumorigenesis and metastasis in various cancer types by affecting the expression of its targets. In the present study, the role of miR-32 (miR-32-5p) in OC was explored. Reverse transcription-quantitative PCR results showed that miR-32 expression was significantly upregulated in both OC tissues and cell lines. Inhibition of miR-32 by transfection with miR-32 inhibitor in OC cells markedly suppressed cell proliferation, migration and invasion. In addition, a luciferase assay showed that suppressor of morphogenesis in genitalia 1 (SMG1) is a direct target of miR-32, and interference in SMG1 expression with transfection of SMG1 small hairpin RNA restored miR-32-mediated OC cell proliferation, migration and invasion. Taken together, these results indicate that miR-32 may promote OC cell growth and motility by targeting SMG1. The data of the present study suggest that miR-32 may serve as a potential therapeutic target for OC treatment in the future.

Upregulation of lncRNA AB073614 functions as a predictor of epithelial ovarian cancer prognosis and promotes tumor growth in vitro and in vivo.

BACKGROUNDS: Upregulation of lncRNA AB073614 is found in some cancer types and involved in tumor development and progression including ovarian cancer. However, the clinical value and functional role of lncRNA AB073614 in epithelial ovarian cancer (EOC) still needed to be investigated. METHODS: We examined lncRNA AB073614 expression using quantitative real time polymerase chain reaction (qRT-PCR) in 75 paired of EOC tissue samples and adjacent normal tissues. Association of lncRNA AB073614 expression with overall survival (OS) was evaluated using Kaplan-Meier analysis. Univariate and multivariate analysis of factors associated with OS were assessed in EOC patients. After lncRNA AB073614 knockdown using siRNAs, the cell viability and cell colony forming assays were performed. Western blot analysis was used to assess relative protein expression. RESULTS: In present study, we demonstrated that lncRNA AB073614 was significantly upregulated in ovarian cancer tissues compared to adjacent normal tissues in patients. Higher lncRNA AB073614 expression significantly associated with tumor size, lymph node invasion, FIGO stage, and shorter OS rate of EOC patients. Furthermore, multivariate Cox regression analysis results showed that higher lncRNA AB0736141 was identified as an independent risk factor of OS in EOC patients. Moreover, we demonstrated that lncRNA AB0736141 knockdown suppressed EOC cell proliferation ability and cell colony formation in vitro. In vivo, we showed that AB0736141 knockdown suppressed tumor growth. We also revealed that lncRNA AB0736141 knockdown inhibited the PTEN/PI3K/AKT signaling pathway in EOC. CONCLUSIONS: Thus, these results indicated that LncRNA AB073614 may serve as a prognostic biomarker and potential target of treatment for EOC.

Association of early menopause with angiographically-derived SYNTAX score: Observational study.

Association of early menopause with increased risk of cardiovascular events has been confirmed in previous studies. SYNTAX score (SX-score) can comprehensively quantify severity of coronary artery disease (CAD) and predict the outcomes of patients with CAD. However, the association of early menopause with SX-score has never been reported.We prospectively included 1875 consecutive postmenopausal patients who underwent coronary angiography (CAG) and were angiographically diagnosed with CAD from January 2011 to December 2013. SX-score was calculated using the SX-score algorithm based on diagnostic angiogram. Ordinal logistic regression analysis was used to investigate the association between early menopause and SX-score.Patients with early menopause were more likely to have a history of hypertension, diabetes, hyperlipidemia, and less likely to smoking. Besides, they have higher fasting glucose, hemoglobin A1C (HbA1c), total cholesterol (TC), low-density lipoprotein (LDL), triglyceride (TG), and body mass index (BMI) compared with the patients without early menopause. Moreover, patients with early menopause have higher SX-score and multi-vessel diseases. Ordinal logistic regression analysis showed that age, hypertension, diabetes, and early menopause exerted independent influences on SX-score. The patients undergone oophorectomy, early menopause was highly associated with SX-score.Early menopause was an independent predictor of SX-score in postmenopausal patients with CAD.

miRNA­145 inhibits myocardial infarction­induced apoptosis through autophagy via Akt3/mTOR signaling pathway in vitro and in vivo.

The present study investigated the effects of micro (mi)RNA­145 on acute myocardial infarction (AMI) and the potential underlying mechanism. A total of 6 AMI and 6 normal rat tissues were investigated for the present study. It was demonstrated that miRNA­145 expression was downregulated in the AMI rat model, compared with the control group. Downregulation of miRNA­145 increased cardiac cell apoptosis, suppressed phosphorylated (p)­RAC­Î³ serine/threonine­protein kinase (Akt3) and p­mechanistic target of rapamycin (mTOR) protein expression levels and suppressed autophagy in an in vitro model of AMI. However, overexpression of miRNA­145 decreased cardiac cell apoptosis, induced p­Akt3 and p­mTOR protein expression and promoted autophagy in the in vitro model of AMI. The inhibition of Akt3 (GSK2110183, 1 nM) decreased the effect of the miRNA­145 upregulation on cell apoptosis in the in vitro model of AMI. Chloroquine diphosphate (5 µM) inhibited the regulatory effect of miRNA­145 upregulation on autophagy to adjust cell apoptosis, in the in vitro model of AMI. The results of the present study demonstrate that miRNA­145 inhibits myocardial infarction­induced apoptosis via autophagy associated with the Akt3/mTOR signaling pathway in vivo and in vitro.

Long noncoding RNA UFC1 is activated by E2F1 and exerts oncogenic properties by functioning as a ceRNA of FOXP3.

Cervical cancer is one of the most common gynecologic cancers around the world. Long noncoding RNAs (lncRNAs) are considered to be important regulators of some biological processes. Recently, it has been reported that linc-UFC1 is a putative oncogene in some cancers. However, the functional roles of linc-UFC1 have not been investigated in cervical cancer. Here, it was demonstrated that linc-UFC1 expression was significantly increased in cervical cancer tissues, and its overexpression was associated with the poor survival of patients with cervical cancer. Loss-of-function assays indicated that linc-UFC1 exerted as an oncogene because it promoted the growth and metastasis of cervical cancer cells in vitro and in vivo. Mechanistic investigations revealed that linc-UFC1 upregulated FOXP3 expression through competitively binding miR-34a. Finally, luciferase reporter and chromatin immunoprecipitation (ChIP) assays provided evidence that E2F1 could directly bind to the linc-UFC1 promoter region and enhance its transcription. Taken together, our findings indicate that the linc-UFC1 expression signature may serve as a novel biomarker for the diagnosis and prognosis of cervical cancer, and it is also highlighted that the E2F1-linc-UFC1/miR-34a/FOXP3 axis may be a potentially therapeutic target of cervical cancer.

Long noncoding RNA lncBRM facilitates the proliferation, migration and invasion of ovarian cancer cells via upregulation of Sox4.

Ovarian cancer (OC) is one of the most fatal gynecological cancer in women worldwide. Long noncoding RNA (lncRNA) lncBRM was found to be associated with the progression and prognosis of hepatocellular carcinoma (HCC). However, the expression level, clinical significance and functions in OC tumorigenesis and progression remain unclear. Our present research demonstrated that lncBRM expression was significantly increased in OC tissues. Upregulation of lncBRM expression was correlated with histological grade, FIGO stages, lymph node metastasis and poor prognosis of patients with OC. Functional assays showed that lncBRM positively regulated cell proliferation, migration and invasion in OC. Moreover, lncBRM upregulated Sox4 by competitively binding miR-204. Together, lncBRM functions as an oncogene in OC and can be a promising therapeutic target for OC treatment.

The long non-coding RNA lncFOXO1 suppresses growth of human breast cancer cells through association with BAP1.

Breast cancer, one of the common cancers of women, is the leading cause of death among women below the age of 50 years in western countries. Long non-coding RNAs (lncRNAs) have been shown to be involved in diverse biological processes, both physical and pathological. However, to date, only a few lncRNAs have been functionally identified in breast cancer, and the overall pathophysiological contributions of lncRNAs to breast cancer remain largely unknown. In the present study, we identified a novel lncRNA termed lncFOXO1 through microarray screening. lncFOXO1 is significantly decreased in breast cancer tissues and cell lines and downregulation of lncFOXO1 expression associates with poorer overall survival. Functional assays demonstrated its suppressive role in breast cancer in vivo and in vitro. Mechanistically, lncFOXO1 suppressed the growth of breast cancer by increasing FOXO1 transcription. Moreover, we found that lncFOXO1 associated with BRCA-1-associated protein 1 (BAP1) and regulates its binding and the level of mono-ubiquitinated H2A at K119 (ubH2AK119) at FOXO1 promoter.

Associations of proteins relevant to MAPK signaling pathway (p38MAPK-1,HIF-1 and HO-1) with coronary lesion characteristics and prognosis of peri-menopausal women.

BACKGROUND: The present study was intended to explore whether three proteins within MAPK signaling pathway (i.e. p38MAPK-1, HIF-1 and HO-1) were correlated with peri-menopausal women's coronary lesion features and prognosis. METHODS: Altogether 1449 peri-menopausal women were divided into non-coronary artery disease (CAD) group (n = 860) and CAD group (n = 589), including 167 pre-menopausal CAD populations and 422 post-menopausal CAD populations. General information about CAD risk parameters were gathered, including age, family history of CAD or hypertension or diabetes mellitus, bilirubin, cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and so on. Coronary angiography results were judged, and CAD score was calculated with application of Genisin scoring method. Besides, detection of MAPK-1 levels was implemented with Strept Avidin-Biotin Complex (SABC) method, while HIF-1 and HO-1 expressions in the serum were determined utilizing ELISA detection kit. Correlations among protein expressions, characteristics of coronary lesions and prognosis of CAD populations were finally evaluated. RESULTS: Hypertension, hyperlipoidemia, diabetes and smoking history were more prevalent among postmenopausal CAD women than premenopausal CAD women (P < 0.05). Furthermore, postmenopausal women seemed to be significantly associated with multiple (i.e. double and triple) vessel lesions and severe lesion types (type B and C), when compared with premenopausal CAD group (P < 0.05). Similarly, remarkably elevated expressions of p38MAPK-1, HIF-1 and HO-1 were found within postmenopausal CAD populations in comparison to premenopausal ones (P < 0.05). The internal CysC, hs-CRP, TG and LDL-C concentrations all accorded with the following tendency: postmenopausal CAD women > premenopausal CAD women > non-CAD women. Moreover, p38MAPK-1, HIF-1 and HO-1 expressions were up-regulated with increasing number of vessel lesions and severity of coronary lesions among peri-menopausal women. Besides, among both pre-menopausal and post-menopausal CAD groups, positive correlations could be observed between MAPK-1 and TG (r s = 0.271; r s = 0.476), between HIF-1α and LDL-C (r s = 0.077; r s = 0.470), as well as between HO-1 and CysC (r s = 0.492; r s = 0.190) or hs-CRP (r s = 0.569; r s = 0.542) (all P < 0.05). MAPK-1, HIF-1α and HO-1 were also, respectively, positively correlated with CysC (r s = 0.415), hs-CRP (r s = 0.137), and TG (r s = 0.142), regarding post-menopausal CAD women (all P < 0.05). Finally, only SBP and TG were regarded as independent risk factors for CAD prognosis (i.e. high Genisin score) among premenopausal women (OR = 1.02, 95%CI: 1.01-1.18, P = 0.043; OR = 1.82, 95%CI: 1.01-3.33, P = 0.047). CONCLUSIONS: Expressions of p38MAPK-1, HIF-1 and HO-1 could serve as predictive roles for coronary lesions among peri-menopausal women.

High Expression of Cullin7 Correlates with Unfavorable Prognosis in Epithelial Ovarian Cancer Patients.

Ubiquitin ligase Cullin7 has been has been suggested to act as an oncogene in some tumors; however, the prognostic role of Cullin7 has not been evaluated in cancer patients. In this study, we observed that the expression of Cullin7 mRNA was significantly higher in epithelial ovarian cancer (EOC) compared with normal ovarian surface tissues. In addition, Cullin7 expression was related to FIGO stage (p = .001) and lymph node metastasis (p = .033). Furthermore, Cullin7 overexpression inhibited the migration and invasion of ovarian cancer cells. These results suggest that Cullin7 may serve as an indicator of poor prognosis in patients with EOC.

MALAT1-miR-124-RBG2 axis is involved in growth and invasion of HR-HPV-positive cervical cancer cells.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT 1) is a large, infrequently spliced non-coding RNA aberrantly expressed in cervical cancer. But the molecular mechanisms of its oncogenic role are still not quite clear. The present study explored whether there is a competing endogenous RNAs (ceRNAs) mechanism involved in the oncogenic effect of MALAT1. MALAT1 expression was firstly verified in high-risk human papillomavirus (HR-HPV)-positive tumor tissues and cell lines. Its regulation over miR-124 and the downstream target of miR-124 in regulation of growth, invasion, and apoptosis of the cancer cells are also studied. Findings of this study confirmed higher MALAT1 expression in HR-HPV (+) cervical cancer. Knockdown of endogenous MALAT1 significantly reduced cell growth rate and invasion and increased cell apoptosis of Hela and siHa cells. Besides, knockdown of MALAT1 increased the expression of miRNA-124, while ectopic expression of miR-124 decreased MALAT1 expression. In addition, we also verified a direct interaction between miR-124 and 3'UTR of GRB2. MALAT1 can indirectly modulate GRB2 expression via competing miR-124. Knockdown of GRB2 reduced cell invasion and increased cell apoptosis. In conclusion, MALAT1 can promote HR-HPV (+) cancer cell growth and invasion at least partially through the MALAT1-miR-124-RBG2 axis. This finding might provide some useful evidence about the lncRNA interaction regulatory network in tumorigenesis cervical cancer.

miR-375 Modulates Radiosensitivity of HR-HPV-Positive Cervical Cancer Cells by Targeting UBE3A through the p53 Pathway.

BACKGROUND: Prediction of radioresistance of HR-HPV-positive (+) cervical cancer, especially before the course of radiotherapy, is quite beneficial to develop an optimal treatment strategy for individual patients. Unfortunately, the mechanisms responsible for radioresistance of cervical cancer are still largely unexplored. HR-HPV infection leads to a series of changes to normal biophysical process, including miRNAs expression. In this study, we explored the association between miR-375 and radioresistance in HR-HPV (+) cervical cancer. MATERIAL AND METHODS: qRT-PCR analysis was performed to determine miR-375 expression in HR-HPV-positive (+) cervical cancer patients and in HPV-16-positive SiHa and HPV-18-positive HeLa cervical cancer cell lines. The influence of miR-375 on radiosensitivity and the downstream regulative network were further explored in the cell line models. RESULTS: The results verified a putative binding site between miR-375 and UBE3A. miR-375 overexpression could significantly reduce UBE3A expression. UBE3A knockdown led to significantly reduced cell survival under radiation treatment. miR-375 promoted radiosensitivity of HR-HPV (+) cancer through decreasing p53 degradation and thereby increasing radiation-induced apoptosis. CONCLUSIONS: The miR-375-UBE3A axis is important in modulating radiosensitivity of HR-HPV (+) cervical cancer.

miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1.

Although multiple miRNAs are found involved in radioresistance development in HR-HPV positive (+) cervical cancer, only limited studies explored the regulative mechanism of the miRNAs. miR-21 is one of the miRNAs significantly upregulated in HR-HPV (+) cervical cancer is also significantly associated with radioresistance. However, the detailed regulative network of miR-21 in radioresistance is still not clear. In this study, we confirmed that miR-21 overexpression was associated with higher level of radioresistance in HR-HPV (+) cervical cancer patients and thus decided to further explore its role. Findings of this study found miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells and decrease radiation induced G2/M block and increase S phase accumulation. By using dual luciferase assay, we verified a binding site between miR-21 and 3'-UTR of large tumor suppressor kinase 1 (LATS1). Through direct binding, miR-21 can regulate LATS1 expression in cervical cancer cells. LATS1 overexpression can reverse miR-21 induced higher colony formation rate and also reduced miR-21 induced S phase accumulation and G2/M phase block reduction under radiation treatment. These results suggested that miR-21-LATS1 axis plays an important role in regulating radiosensitivity.

Egg consumption is associated with increased risk of ovarian cancer: Evidence from a meta-analysis of observational studies.

BACKGROUND: The findings of epidemiologic studies on the association between egg consumption and ovarian cancer risk remain conflicting. The aim of this meta-analysis was to investigate whether an association exists between egg intake and ovarian cancer risk in epidemiologic studies. METHODS: A literature search was carried out using PUBMED, EMBASE, and Cochrane Library Central database for all medical literature published in English-language journals up to August 2013. Before meta-analysis, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity analysis were also performed. RESULTS: A total of 12 eligible studies (six case-control studies and six cohort studies) were included, involving 629,453 subjects and 3728 ovarian cancer cases. We found that high egg intake (comparing the highest with the lowest category) was associated with a significant increased risk of ovarian cancer (RR = 1.21, 95% CI [1.06, 1.38]). When we examined whether the associations differed by study type, statistically significant effect of egg intake on ovarian cancer was observed among case-control studies (RR = 1.22, 95% CI [1.03, 1.43]), but not among cohort studies (RR = 1.20, 95% CI [0.97, 1.48]). CONCLUSIONS: Our findings suggest that egg consumption may increase ovarian cancer risk. Additional studies, especially large prospective cohort studies, are warranted to confirm the findings.