High-risk human papillomavirus oncoproteins E6 and E7 are the major etiological factors of cervical cancer but are insufficient for malignant transformation of cervical cancer. Dysregulated alternative splicing, mainly ascribed to aberrant splicing factor levels and activities, contributes to most cancer hallmarks. However, do E6 and E7 regulate the expression of splicing factors? Does alternative splicing acts as an “accomplice” of E6E7 to promote cervical cancer progression? Here, we identified that the splicing factor SRSF10, which promotes tumorigenesis of cervix, was upregulated by E6E7 via E2F1 transcriptional activation. SRSF10 modulates the alternate terminator of interleukin-1 receptor accessory protein exon 13 to increase production of the membrane form of interleukin-1 receptor accessory protein. SRSF10-mediated mIL1RAP upregulates the expression of the “don’t eat me” signal CD47 to inhibit macrophage phagocytosis by promoting nuclear factor-κB activation, which is pivotal in inflammatory, immune, and tumorigenesis processes. Altogether, these data reveal a close relationship among HPV infection, alternative splicing and tumor immune evasion, and also suggests that the SRSF10-mIL1RAP-CD47 axis could be an attractive therapeutic target for the treatment of cervical cancer.

Background: The severity of menopausal symptoms can vary according to ethnicity and geography. Two common menopausal symptom scales, the modified Kupperman Index (KI) and the Menopausal Rating Scale (MRS), are accepted internationally. In this study, we evaluated the correlation between these scales and their relevance to women in the People's Republic of China. Methods: We enrolled treatment-naïve women who visited the menopause outpatient department at a major teaching hospital in Shanghai, People’s Republic of China. The women were required to complete two questionnaires, ie, the modified KI and the MRS. We assessed the correlation between the tools using a correlation analysis. Results: We enrolled 277 women of average age 51.5 ± 4.8 years. There was a strong positive correlation between total scores on the modified KI and the MRS (0.74, 95% confidence interval 0.69–0.79) and subscores for the somatic and psychological domains (0.74 and 0.77, respectively), with a moderate correlation for urogenital symptoms. According to the modified KI, 15 (5.4%) women were categorized as asymptomatic, and when using the MRS, 33 (11.9%) were categorized as asymptomatic. Women categorized as having none/minimal symptoms by the MRS were diagnosed as having mild to severe symptoms using the modified KI. The highest agreement (74%) was found when symptoms were moderate. Conclusion: The modified KI and the MRS do correlate in Chinese women, but the modified KI is more likely to identify menopausal symptoms than the MRS in screening if there is doubt about the diagnosis of menopause.

Background: Cardiovascular disease is the leading cause of mortality in postmenopausal women. Follicle‐stimulating hormone ( FSH ) shows negative associations with obesity and diabetes mellitus in postmenopausal women. We aimed to study the associations between FSH and 10‐year risk of atherosclerotic cardiovascular disease ( ASCVD ) in postmenopausal women. Methods and Results: SPECT ‐China (the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors) is a 22‐site, population‐based study conducted during 2014–2015. This study included 2658 postmenopausal women. A newly developed effective tool for 10‐year ASCVD risk prediction among Chinese was adopted. Regression analyses were performed to assess the relationship among FSH , 10‐year ASCVD risk, and multiple cardiometabolic risk factors. With the increase in FSH quartiles, the mean 10‐year ASCVD risk in postmenopausal women decreased from 4.9% to 3.3%, and most metabolic parameters were significantly ameliorated (all P for trend <0.05). In regression analyses, a 1‐ SD increment in ln‐ FSH was negatively associated with continuous (B −0.12, 95% confidence interval, −0.16, −0.09, P <0.05) and categorical (odds ratio 0.65, 95% confidence interval, 0.49, 0.85, P <0.05) 10‐year ASCVD risk. These significant associations existed in subgroups with or without medication use, obesity, diabetes mellitus, hypertension, and dyslipidemia. Body mass index and waist circumference (both B −0.35, 95% confidence interval, −0.40, −0.30, P <0.05) had the largest associations of all metabolic measures, and blood pressure had the smallest association. Conclusions: Serum FSH levels were negatively associated with 10‐year ASCVD risk in postmenopausal women. Among cardiometabolic factors, obesity indices had the largest associations with FSH . These results indicated that a low FSH might be a risk factor or a biomarker for cardiovascular disease risk in postmenopausal women.

Endometrial carcinoma (EC) is one of the most common gynecological malignancies among women. Maternal embryonic leucine Zipper Kinase (MELK) is upregulated in a variety of human tumors, where it contributes to malignant phenotype and correlates with a poor prognosis. However, the biological function of MELK in EC progression remains largely unknown. We explored the MELK expression in EC using TCGA and GEO databases and verified it using clinical samples by IHC methods. CCK-8 assay, colony formation assay, cell cycle assay, wound healing assay and subcutaneous xenograft mouse model were generated to estimate the functions of MELK and its inhibitor OTSSP167. qRT-PCR, western blotting, co-immunoprecipitation, chromatin immunoprecipitation and luciferase reporter assay were performed to uncover the underlying mechanism concerning MELK during the progression of EC. MELK was significantly elevated in patients with EC, and high expression of MELK was associated with serous EC, high histological grade, advanced clinical stage and reduced overall survival and disease-free survival. MELK knockdown decreased the ability of cell proliferation and migration in vitro and subcutaneous tumorigenesis in vivo. In addition, high expression of MELK could be regulated by transcription factor E2F1. Moreover, we found that MELK had a direct interaction with MLST8 and then activated mTORC1 and mTORC2 signaling pathway for EC progression. Furthermore, OTSSP167, an effective inhibitor, could inhibit cell proliferation driven by MELK in vivo and vitro assays. We have explored the crucial role of the E2F1/MELK/mTORC1/2 axis in the progression of EC, which could be served as potential therapeutic targets for treatment of EC. This research was supported by National Natural Science Foundation of China (No:81672565), the Natural Science Foundation of Shanghai (Grant NO:17ZR1421400 to Dr. Zhihong Ai) and the fundamental research funds for central universities (No: 22120180595).

3β-Hydroxysteroid-Δ24 reductase (DHCR24), the final enzyme of the cholesterol biosynthetic pathway, has been associated with urogenital neoplasms. However, the function of DHCR24 in endometrial cancer (EC) remains largely elusive. Here, we analyzed the expression profile of DHCR24 and the progesterone receptor (PGR) in our tissue microarray of EC (n = 258), the existing EC database in GEO (Gene Expression Omnibus), and TCGA (The Cancer Genome Atlas). We found that DHCR24 was significantly elevated in patients with EC, and that the up-regulation of DHCR24 was associated with advanced clinical stage, histological grading, vascular invasion, lymphatic metastasis, and reduced overall survival. In addition, DHCR24 expression could be induced by insulin though STAT3, which directly binds to the promoter elements of DHCR24, as demonstrated by ChIP-PCR and luciferase assays. Furthermore, genetically silencing DHCR24 inhibited the metastatic ability of endometrial cancer cells and up-regulated PGR expression, which made cells more sensitive to progestin. Taken together, we have demonstrated for the first time the crucial role of the insulin/STAT3/DHCR24/PGR axis in the progression of EC by modulating the metastasis and progesterone response, which could serve as potential therapeutic targets for the treatment of EC with progesterone receptor loss.