G-quadruplex formation within the promoter region of HSPB2 and its effect on transcription.

G-rich sequences in DNA and RNA tend to fold into stable secondary structures called G-quadruplexes. Except for the telomere region, G-quadruplex-forming sequences are widely present in gene promoters and have been implicated in transcriptional regulation. Single nucleotide polymorphisms (SNPs) can disrupt the G-quadruplex structure of a gene promoter. In this study, we confirmed the promoter of HSPB2, a cancer-related gene, tends to form an unusual DNA secondary structure. The dual luciferase assay revealed that the SNP rs2234704 in the HSPB2 promoter with a single G > A mutation increased the transcriptional activity of the HSPB2 promoter. Circular dichroism and native PAGE revealed that the G-rich strand of the DNA in this promoter preferred to form a parallel G-quadruplex, which could be destabilized by the SNP rs2234704 (G > A) mutation. Furthermore, we found that the SNP rs2234704 (G > A) greatly increased and influenced the overexpression of HSPB2 in breast cancer samples. These results suggest SNP rs2234704 (G > A) may play a role in the occurrence of breast cancer by destroying the G-quadruplex structure and promoting the expression of HSPB2.

Comprehensive evaluation of the effect of inactivated SARS-CoV-2 vaccination on female fertility: A retrospective cohort study.

Fear of possible negative effects of coronavirus disease 2019 (COVID-19) vaccine on fertility is the main reason for vaccine hesitancy among the public especially women of childbearing age. Despite the high coverage of COVID-19 vaccination in China, more scientific evidence is still needed to address their concerns and guide fertility counseling and management in the future. Herein, we performed a retrospective cohort study at a single large center for reproductive medicine in China between August 2020 and May 2023. Patients aged 20-42 years with no history of laboratory-confirmed COVID-19 were included and categorized into different groups according to their vaccination status. The serum sex hormone levels, anti-Müllerian hormone concentrations, embryo quality, and pregnancy outcomes were evaluated and compared among them. We found there were no significant differences in the concentrations of follicle-stimulating hormone, luteinizing hormone and progesterone between the unvaccinated, first-dose, second-dose, and booster vaccinated groups. However, the estradiol showed a highly significant increase in the one-dose vaccinated group compared with its levels in other groups. Among unvaccinated and either vaccinated patients, anti-Müllerian hormone levels were comparable (p = 0.139). The number of oocytes retrieved, fertilization rate and good-quality embryo rate were all similar between each group of in vitro fertilization and intracytoplasmic sperm injection. No significant differences were observed regarding other laboratory parameters. Moreover, the vaccination status of infertile couples did not exert any adverse effect on the pregnancy outcomes in all assisted reproductive technologies cycles. In short, we comprehensively evaluated the reproductive safety of inactivated severe acute respiratory syndrome coronavirus 2 vaccine and found any dose of vaccination wouldn't negatively affect female fertility parameters such as sex hormone levels and ovarian reserve. Moreover, this is the first study to complete the live birth follow-up of the cohort after receiving inactivated severe acute respiratory syndrome coronavirus 2 vaccine, further dispelling the misconception and providing reassurance for decision-making by clinicians.

Effects of inactivated SARS-CoV-2 vaccination on male fertility: A retrospective cohort study.

Numerous studies have revealed severe damage to male fertility from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, raising concerns about the potential adverse impact on reproductive function of the coronavirus disease 2019 (COVID-19) vaccine developed based on the virus. Interestingly, there are several researchers who have studied the impact of the COVID-19 mRNA vaccine since then but have come up with conflicting results. As a near-ideal candidate for mass immunization programs, inactivated SARS-CoV-2 vaccine has been widely used in many countries, particularly in less wealthy nations. However, little is known about its effect on male fertility. Here, we conducted a retrospective cohort study at a single large center for reproductive medicine in China between December 2021 and August 2022. Five hundred and nineteen fertile men with no history of laboratory-confirmed COVID-19 were included and categorized into four groups based on their vaccination status: unvaccinated group (n = 168), one-dose vaccinated group (n = 8), fully vaccinated group (n = 183), and booster group (n = 160). All of them underwent a semen analysis and most had serum sex hormone levels tested. There were no significant differences in all semen parameters and sex hormone levels between the unvaccinated group and either vaccinated group. To account for possible vaccination-to-test interval-specific changes, sub-analyses were performed for two interval groups: ≤90 and >90 days. As expected, most of the semen parameters and sex hormone levels remained unchanged between the control and vaccinated groups. However, participants in vaccinated group (≤90 days) have decreased total sperm motility and increased follicle-stimulating hormone level compared with the ones in unvaccinated group. Moreover, some trends similar to those found during COVID-19 infection and recovery were observed in our study. Fortunately, all values are within the normal range. In addition, vaccinated participants reported few adverse reactions. No special medical intervention was required, and no serious adverse reactions happened. Our study suggests that inactivated SARS-CoV-2 vaccination does not impair male fertility, possibly due to the low frequency of adverse effects. This information reassures young male population who got this vaccine worldwide, and helps guide future vaccination efforts.

Clinical Effects of the COVID-19 Pandemic Among the Uninfected Pregnant Women - 6 PLADs, China, 2019-2020.

SUMMARY: What is already known about this topic? The coronavirus disease 2019 (COVID-19) pandemic potentially affected prenatal care quality and maternal and fetal outcomes globally.What is added by this report? During COVID-19 pandemic period, the rates of caesarean sections (CS) and preterm birth for uninfected pregnant women increased slightly in areas that were relatively severely impacted by the pandemic in China. The overall number of prenatal examinations did not dramatically decrease, while the eligible examinations significantly decreased in Hubei Province.What are the implications for public health practice? Routine prenatal examinations had been well maintained during the pandemic period in China. In the future, in-time prenatal examinations should be provided to improve the quality of screening and management of high-risk pregnancy under pandemic-affected circumstances. Psychological counseling and transfer treatment channels should be strengthened for pregnant women during lockdown period.

[Variant analysis of SOX5 gene in a Lamb-Shaffer syndrome family].

OBJECTIVE: To explore the genetic basis for a case of Lamb-Shaffer syndrome. METHODS: Genomic DNA was extracted from peripheral blood samples and subjected to whole exome sequencing(WES). Suspected variant was verified by Sanger sequencing. RESULTS: The patients was found to harbor a heterozygous c.1495delA(p.Thr499Glnfs*5) frameshift variant of the SOX5 gene by WES. Sanger sequencing confirmed that the same variant was a de novo variant. Based on the American College of Medical Genetics and Genomics guidelines, c.1495delA(p.Thr499Glnfs*5) variant of the SOX5 gene was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION: The c.1495delA(p.Thr499Glnfs*5) variant of the SOX5 gene probably underlies the Lamb-Shaffer syndrome in this patient.

Associations between endocrine-disrupting heavy metals in maternal hair and gestational diabetes mellitus: A nested case-control study in China.

BACKGROUND: Exposure to environmental endocrine disruptors (EDCs) may lead to abnormal glucose metabolism and, potentially, gestational diabetes mellitus (GDM). OBJECTIVE: We investigated the association between five endocrine-disrupting heavy metals (EDHMs), i.e., arsenic (As), cadmium (Cd), lead (Pb), mercury (Hg), and tin (Sn), in maternal hair and the risk of GDM. METHODS: We conducted a nested case-control study including 335 GDM cases and 343 controls without GDM based on a prospective birth cohort established in Beijing, China. Concentrations of EDHMs were analyzed in maternal hair. Log-binomial regression and multiple linear regression were used to estimate the associations between the hair concentrations of single metals and the risk of GDM, while weighted quantile sum (WQS) regression for their mixed effects. RESULTS: The median concentrations of Hg (0.442 vs. 0.403 µg/g) and Sn (0.171 vs. 0.140 µg/g) in the case group were significantly higher than those in the control group. No differences were found between the two groups for the other three metals. After adjusting for confounders, the prevalence ratio (PR; highest vs. lowest tertile) of GDM risk for Hg was 1.27 (95% confidence interval [CI]: 1.05-1.54), while that for Sn was 1.26 (95% CI: 1.04-1.53). Among women with a body mass index < 24 kg/m2, the PR (highest vs. lowest tertile) of GDM for Sn was 1.38 (95% CI: 1.09-1.75). The effect of exposure to the five EDHMs on the risk of GDM was estimated by WQS regression: Sn and Hg made the largest contributions to the WQS index (40.9% and 40.3%, respectively). CONCLUSION: High maternal levels of EDHMs, particularly Sn and Hg, may promote the development of GDM.

AR-mTOR-SRF Axis Regulates HMMR Expression in Human Prostate Cancer Cells.

The elevated expression of the hyaluronan-mediated motility receptor (HMMR) is known to be highly associated with tumor progression in prostate cancer, but the molecular mechanisms underlying the regulation of HMMR expression remain unclear. Here, we report that mammalian target of rapamycin (mTOR) is a key regulator of HMMR expression, for which its kinase activity is required. Pharmacological inhibitors of mTOR, such as rapamycin and Torin2, markedly suppressed the mRNA level as well as the protein level of HMMR in LNCaP and PC-3 cells. Our data demonstrate that such regulation occurs at the transcription level. HMMR promoter reporter assays revealed that the transcription factor SRF is responsible for the mTOR-mediated transcriptional regulation of HMMR gene. Consistently, the suppression of HMMR expression by Torin2 was noticeably reversed by the overexpression of SRF. Moreover, our findings suggest that the SRF binding sites responsible for the transcriptional regulation of HMMR through the mTOR-SRF axis are located in HMMR promoter sequences carrying the first intron, downstream of the translational start site. Furthermore, the upregulation of HMMR by DHT was abolished by stimulation with rapamycin, prior to DHT treatment, suggesting that mTOR activity is required for the induction of HMMR expression by androgen. Collectively, our study provides new mechanistic insights into the role of mTOR/SRF/AR signaling in HMMR regulation in prostate cancer cells.

Contribution of Temperature Increase to Restrain the Transmission of COVID-19.

The COVID-19 outbreak has already become a global pandemic and containing this rapid worldwide transmission is of great challenge. The impacts of temperature and humidity on the COVID-19 transmission rate are still under discussion. Here, we elucidated these relationships by utilizing two unique scenarios, repeated measurement and natural experiment, using the COVID-19 cases reported from January 23 - February 21, 2020, in China. The modeling results revealed that higher temperature was most strongly associated with decreased COVID-19 transmission at a lag time of 8 days. Relative humidity (RH) appeared to have only a slight effect. These findings were verified by assessing SARS-CoV-2 infectivity under the relevant conditions of temperature (4°C-37°C) and RH (> 40%). We concluded that temperature increase made an important, but not determined, contribution to restrain the COVID-19 outbreak in China. It suggests that the emphasis of other effective controlling polices should be strictly implemented to restrain COVID-19 transmission in cold seasons.

LIF in embryo culture medium is a predictive marker for clinical pregnancy following IVF-ET of patients with fallopian tube obstruction.

Leukemia inhibitory factor (LIF) has played a vital role in a series of reproductive events, including follicle growth, embryo growth and differentiation. However, it is unclear whether the level of LIF in embryo culture medium can be used as a marker for clinical pregnancy. In this study, we aimed to investigate whether LIF level in embryo culture medium can act as a predictive marker for pregnancy outcome of in vitro fertilization-embryo transfer (IVF-ET) in infertile women due to tubal problems. A total of 208 infertile women due to tubal problems underwent IVF-ET treatment. The women were divided into two groups according to whether they were clinically pregnant. The level of LIF in the embryo culture medium was measured, and the correlation between LIF level and embryo quality and clinical pregnancy outcome was analyzed. The embryo culture medium was collected on the day of blastocyst transplantation. Compared to non-pregnant group, LIF level in the embryo culture medium on the day of blastocyst transplantation was significantly higher in the pregnant group. LIF level in the embryo culture medium may be used as a non-invasive auxiliary biomarker for predictive clinical pregnancy in infertile women with tubal problems that using single blastocyst transfer method.

Body mass index (BMI) is associated with serum thyroid-stimulating hormone (TSH) level in infertile women: a cross-sectional study.

Studies suggest that there is a relationship between body mass index (BMI) and thyroid-stimulating hormone (TSH) levels. But conflicting evidence exists regarding the relationship between the two variables. Moreover, thyroid function is closely related to female fertility and has certain effects on infertility. Therefore, the present study will explore the relationship between BMI and TSH levels in patients with infertility in our center. We retrospectively analyzed relevant indicators of 2,789 in Tubal Factor Infertility patients undergoing assisted reproduction technology from January 2016 to December 2018 in our center in order to analyze the relationship between BMI and serum TSH level. The medical histories of patients were reviewed. The relationship between BMI and TSH was assessed using smooth curve fitting and multivariate regression model. The smoothing curve fitting between BMI and TSH exhibited a non-linear relationship, and the resulting curve exhibited a two-stage change and a breakpoint. By multivariate piecewise linear regression, we found that the TSH level was increased with the increase of BMI when the BMI was greater than 25.3 kg/m2 (ß 0.06, 95% CI 0.02, 0.01; p = 0.0028). In contrast, the TSH level was decreased with the increase of BMI when the BMI was less than 25.3 kg/m2 (ß -0.02, 95% CI -0.05, 0.00; p = 0.0573). Collectively, our study described a non-linear relationship between BMI and TSH level in infertile patients after adjustment of potential confounders. However, such causal relationship between BMI and TSH in infertile women still needs to be further clarified in future investigations.

Simultaneous analysis of typical halogenated endocrine disrupting chemicals and metal(loid)s in human hair.

Hair analysis has been an important approach in evaluating population exposure to various environmental factors. To meet the requirements of human environmental epidemiology studies, we aimed to develop an efficient method for simultaneous analysis of various metal(loid)s and some typical environmental halogenated endocrine disrupting chemicals (hEDCs) (i.e., polychlorinated biphenyls, polybrominated diphenyl ethers, and organochlorine pesticides, as well as some of their hydroxyl substituted metabolites) in a single hair sample. The hair was washed successively with surfactant solutions, methanol solvent, and deionized water to remove impurities attached to the hair surface. Efficiency was comprehensively compared among various washing strategies. The hair sample was further pulverized into fine powder with a median diameter (25th-75th percentile) of 8.6 (5.9-13.5) µm. The hair organic components were extracted by acetonitrile solvent and compared with the microwave-assisted extraction method. The hEDCs in the supernatant acetonitrile phase were quantified by gas chromatography-mass spectrometry, and the metal(loid)s in the precipitate hair were further analyzed by inductively coupled plasma mass spectrometry. Our developed method was further applied to analyze the hair samples of 165 pregnant women. The results showed that particles attached to the surface of the hair could not be washed off completely. However, we proposed a protocol framework to wash hair with relatively high efficience, which includes warm water incubation, and use of surfactant and organic solvent. The recoveries of the concerned hEDCs and metal(loid)s were overall in the range of 80% to 120%. For the women population, the method can efficiently recognize the typical exposure characteristics of the concerned hEDCs and metal(loid)s. Our study significantly ameliorated the deficiencies of the traditional hair washing strategy and developed an efficient method for simultaneous analysis of various metal(loid)s and hEDCs in a single hair sample. This method will provide important support for population complex exposure analysis and facilitate environmental exposome studies.

Aberrant expression of CD13 and stem cell markers in CD133-induced liver cancer in mice.

PURPOSE: The purpose of the study is to identify the Cancer Stem Cells (CSCs) and to determine their expression profiles in different pathological stages of liver cancer by using multiple markers Methods: In this study, the expression profiles of CD133 and CD13, along with those of stem cell markers Oct4 and SOX2, were analyzed using immunohistochemistry and immunoblotting to clarify the character of CSCs in different stages of liver cancer. RESULTS: CD133 liver cancer cells were injected into mice, and the tissues were processed for histology. The histological data revealed the progression of liver cancer. Immunohistochemical analysis showed the strong expression of CD133 in metastatic cancer. In contrast, the expression of CD13 in both primary and metastatic liver cancer was found to be very strong. Interestingly, the expression levels of Oct4 and SOX2 were found to be upregulated in primary tumors, but, in the metastatic stage, their expression was downregulated. The immunoblot analysis also confirmed the same result. CONCLUSIONS: Our findings demonstrate that tumor-suppressor proteins Oct4 and SOX2 have a prominent expression profile in the primary stage of cancer, but, in the metastatic stage, their expression is downregulated, leading to the failure to prevent metastatic cancer.

lncRNA UCA1 Mediates Resistance to Cisplatin by Regulating the miR-143/FOSL2-Signaling Pathway in Ovarian Cancer.

The aim of this study was to explore the roles of the long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) on cisplatin resistance in ovarian cancer and the underlying mechanisms. We investigated the expression of lncRNAs in 3 paired cisplatin-sensitive and cisplatin-resistant tissues of ovarian cancer by microarray analysis. The qRT-PCR analysis was to investigate the expression pattern of UCA1 in cisplatin-resistant ovarian cancer patient tissues and cell lines. Then we examined the effects of UCA1 on cisplatin resistance in vitro and in vivo. In this study, UCA1 was observed to be upregulated in cisplatin-resistant patient tissues and cell lines. Knockdown of UCA1 inhibited cell proliferation and promoted the cisplatin-induced cell apoptosis in ovarian cancer cells. Then we demonstrated that repressed UCA1 promoted the miR-143 expression and miR-143 could bind to the predicted binding site of UCA1. Furthermore, we found that miR-143 displayed its role via modulating the FOSL2 expression. Importantly, we demonstrated that UCA1 was upregulated in serum exosomes from cisplatin-resistant patients. In summary, our study demonstrated that UCA1 modulates cisplatin resistance through the miR-143/FOSL2 pathway in ovarian cancer.

Potential effect of germanium exposure on the risk of influenza-like illness in housewives in Shanxi Province, China.

Few studies have examined the relationship between exposure to germanium (Ge) and the risk of influenza-like illness (ILI). Therefore, we investigated the association of Ge exposure and its interaction with single nucleotide polymorphisms (SNPs) related to Phase II metabolism on ILI risk among housewives in Shanxi Province, northern China. This cross-sectional study enrolled 373 housewives. Information on the housewives' characteristics and the frequency of ILI was collected by questionnaire. We analyzed the Ge concentrations in hair samples taken from near the scalp at the back of the head. Blood samples were used to identify SNPs related to Phase II metabolism. The results suggested that the hair Ge concentration was associated with ILI risk with an adjusted odds ratio and 95% confidence interval of 2.59 (1.61-4.19). A significant dose-response relationship was observed without or with adjusting for confounders. We did not observe any interaction effect between the hair Ge concentration and the SNPs on ILI risk. We found that high dietary consumption of meat and fried foods was positively correlated with the hair Ge concentration. Therefore, chronic Ge exposure may be a risk factor for an increased frequency of ILI in housewives.

Leukaemia inhibitory factor in serum and follicular fluid of women with polycystic ovary syndrome and its correlation with IVF outcome.

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, ovarian dysfunction and polycystic ovarian morphology. Leukaemia inhibitory factor (LIF) affects many reproductive activities, including follicular development, embryo implantation and growth. The aim of this study was to evaluate LIF concentrations in serum and follicular fluid of women with PCOS and controls who underwent IVF with embryo transfer (IVF-ET). Serum and follicular fluid LIF concentrations were lower in women with PCOS compared with controls. Oestradiol concentrations in follicular fluid were higher in PCOS subjects compared with controls. LIF concentrations in serum (r = 0.6263, P < 0.05) and follicular fluid (r = 0.7093, P < 0.05) were negatively correlated with oestradiol concentration in the PCOS group. LIF concentrations in follicular fluid showed no difference between women who conceived and women who did not in both PCOS and control groups. However, LIF concentrations in embryo culture medium were higher in women who conceived following IVF compared with women who did not, in combined PCOS and control groups. The findings indicate that low LIF concentrations in serum and follicular fluid may contribute to disordered folliculogenesis in PCOS. LIF concentrations in embryo culture medium may predict the outcome of IVF treatment.

Protective Effect of Yang Mi Ryung® Extract on Noise-Induced Hearing Loss in Mice.

Noise-induced hearing loss (NIHL) results from the damage of the delicate hair cells inside the ear after excessive stimulation of noise. Unlike certain lower animals such as amphibians, fishes, and birds, in humans, hair cells cannot be regenerated once they are killed or damaged; thus, there are no therapeutic options to cure NIHL. Therefore, it is more important to protect hair cells from the noise before the damage occurs. In this study, we report the protective effect of Yang Mi Ryung extract (YMRE) against NIHL; this novel therapeutic property of YMRE has not been reported previously. Our data demonstrates that the hearing ability damaged by noise is markedly restored in mice preadministrated with YMRE before noise exposure, to the level of normal control group. Our study also provides the molecular mechanism underlying the protective effect of YMRE against NIHL by showing that YMRE significantly blocks noise-induced apoptotic cell death and reduces reactive oxygen species (ROS) production in cochleae. Moreover, quantitative polymerase chain reaction (qPCR) analysis demonstrates that YMRE has anti-inflammatory properties, suppressing the mRNA levels of TNFα and IL-1ß induced by noise exposure. In conclusion, YMRE could be a useful preventive intervention to prevent hearing impairment induced by the exposure to excessive noise.

MicroRNA-203 Is a Prognostic Indicator in Bladder Cancer and Enhances Chemosensitivity to Cisplatin via Apoptosis by Targeting Bcl-w and Survivin.

Resistance to cisplatin-based chemotherapy is a major cause of treatment failure in advanced bladder cancer (BC) patients. There is increasing evidence that microRNAs are involved in the development and progression of BC. However, little is known about the function of microRNAs in predicting the effect of adjuvant chemotherapy on BC survival and regulating response to cisplatin. To address this issue, we employed RT-qPCR to evaluate the clinical significance of miR-203 expression in 108 tissues of BC patients receiving cisplatin-based adjuvant chemotherapy, and performed in vitro studies to explore chemotherapeutic sensitivity to cisplatin in miR-203 overexpressing BC cells. We found miR-203 levels were significantly lower in BC progression group than non-progression group (P<0.001). ROC curve analysis illustrated miR-203 could significantly distinguish progressed patients from those without progression (P<0.001), yielding an area under the ROC curve of 0.839 (95% CI, 0.756-0.903). Moreover, low miR-203 expression correlated with shortened progression free survival (PFS) and overall survival (OS) of BC patients, and was an independent prognostic factor. Overexpression of miR-203 in 5637 and T24 BC cells could decrease cell viability, enhance cisplatin cytotoxicity, and promote apoptosis. Western blotting and luciferase reporter assay showed Bcl-w and Survivin were direct downstream targets of miR-203. There was also a significant inverse association between miR-203 and Bcl-w or Survivin expression in BC tissues (r = -0.781, -0.740, both P<0.001). In conclusion, decreased miR-203 predicts progression and poor prognosis for BC patients treated with cisplatin-based chemotherapy while miR-203 overexpression can enhance cisplatin sensitization by promoting apoptosis via directly targeting Bcl-w and Survivin.

Periostin expression and its prognostic value for colorectal cancer.

Integrin is important for cell growth, invasion and metastasis, which are frequently observed in malignant tumors. The periostin (POSTN) gene encodes the ligand for integrin, one of the key focal adhesion proteins contributing to the formation of a structural link between the extracellular matrix and integrins. High expression levels of the POSTN gene are correlated with numerous human malignancies. We examined POSTN protein in colorectal cancer specimens from 115 patients by strictly following up using immunohistochemistry. Cytoplasm immunohistochemical staining showed POSTN protein expression in colorectal cancers. The positive expression rate of POSTN protein (59.13%, 68/115) in colorectal cancers was significantly higher than that in adjacent normal colon mucosa (0.47%, 11/109). POSTN over-expression in colorectal cancers was positively correlated with tumor size, differentiation, lymph node metastasis, serosal invasion, clinical stage and five-year survival rates. Further analysis showed that patients with advanced stage colorectal cancer and high POSTN expression levels had lower survival rates than those with early stage colorectal cancer and low POSTN expression levels. Overall, our results showed that POSTN played an important role in the progression of colorectal cancers.

MiR-203 suppresses ZNF217 upregulation in colorectal cancer and its oncogenicity.

Zinc finger protein 217 (ZNF217) is essential for cell proliferation and has been implicated in tumorigenesis. However, its expression and exact roles in colorectal cancer (CRC) remain unclear. In this study, we demonstrated that ZNF217 expression was aberrantly upregulated in CRC tissues and associated with poor overall survival of CRC patients. In addition, we found that ZNF217 was a putative target of microRNA (miR)-203 using bioinformatics analysis and confirmed that using luciferase reporter assay. Moreover, in vitro knockdown of ZNF217 or enforced expression of miR-203 attenuated CRC cell proliferation, invasion and migration. Furthermore, combined treatment of ZNF217 siRNA and miR-203 exhibited synergistic inhibitory effects. Taken together, our results provide new evidences that ZNF217 has an oncogenic role in CRC and is regulated by miR-203, and open up the possibility of ZNF217- and miR-203-targeted therapy for CRC.

Overexpression of miR-223 correlates with tumor metastasis and poor prognosis in patients with colorectal cancer.

The purpose of the study was to investigate microRNA-223 (miR-223) expression in colorectal cancer (CRC) and its relationship with tumorigenesis and disease prognosis. Quantitative real-time PCR was used to measure levels of miR-223 in tumor samples and adjacent non-cancerous tissues from 62 patients undergoing radical resection for the treatment of CRC. The associations between miR-223 expression and patient age, sex, as well as clinicopathologic parameters, such as tumor size, differentiation, location, invasion depth, metastasis, tumor-node-metastasis (TNM) stage, and overall patient survival, were analyzed by Mann-Whitney U and Kruskal-Wallis tests. Kaplan-Meier method and Cox proportional hazards regression analyses were performed to estimate the prognostic factors for patient survival prediction. The expression of miR-223 was significantly upregulated in CRC tissues compared with adjacent non-cancerous tissues (P < 0.05). This overexpression was associated with TNM stage and lymph node and distant metastases, (P < 0.05). Moreover, Kaplan-Meier analysis demonstrated that patients with high miR-223 expression had a poorer overall survival (OS) than those with low miR-223 expression (P = 0.002). Univariate analysis revealed a statistically significant correlation between OS and miR-223 level, histology grade, metastasis and TNM stage (P < 0.001). Furthermore, miR-223 levels and histology grade were independently associated with OS (HR 0.204, 95 % CI 0.101-0.415, P < 0.05 and HR 2.252, 95 % CI 1.429-3.546, P < 0.05, respectively). The overexpression of miR-223 may play an important role in the progression of CRC and can be used as an independent factor to determine CRC prognosis.