MicroRNA-218 (miR-218) has been implicated in the development and progression of multiple cancers. We investigated the role of miR-218 in ovarian cancer progression. We found that miR-218 expression levels were lower in ovarian cancer tissues and cell lines than in adjacent normal tissues or a normal ovarian cell line. miR-218 levels associated with International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis. Exogenous expression of miR-218 inhibited cell proliferation, colony formation, migration, and invasion in vitro and suppressed tumor growth in a tumor-bearing nude mouse model. Runt-related transcription factor 2 (RUNX2) was identified as a direct functional target of miR-218, and its expression was inversely correlated with miR-218 expression in ovarian cancer tissues. RUNX2 overexpression rescued the suppressive effect of miR-218 on ovarian cancer cell proliferation, colony formation, migration, and invasion. These findings highlight an important role played bymiR-218 in the regulation of cancer growth and metastasis, in part by repressing RUNX2, and revealed the potential of miR-218 as a new therapeutic target inovarian cancer.

Emerging studies indicate that long noncoding RNAs (lncRNAs) play crucial roles in ovarian cancer (OC). By analyzing high-throughput data, we found that SNHG17 was highly expressed in multiple OC cohorts. However, its functions in OC were not explored. In this study, lncRNA expression in OC was analyzed by a series of microarray data. The functions of SNHG17 were investigated by various in vitro and in vivo assays. Fluorescence in situ hybridization (FISH), RNA pull-down, chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), and luciferase reporter assays were used to reveal the potential mechanisms involved in the effects of SNHG17. We found that SNHG17 was overexpressed in OC and that the oncogenic transcription factor STAT3 was involved in promoting its expression. In addition, high SNHG17 expression was associated with a poor prognosis in OC. Functional analysis revealed that SNHG17 could promote OC cell growth. Mechanistically, SNHG17 was found to be located predominantly in the cytoplasm. It could regulate expression of CDK6, an important cell-cycle regulator, by acting as a molecular sponge for miR-214-3p. In summary, our study suggested that SNHG17 acted as an oncogene in OC, which might serve as a novel target for OC diagnosis and therapy.

No abstract

The pathogenesis of preeclampsia (PE) is complicated and multiple risk factors have been associated with its occurrence. Still, the underlying molecular mechanisms involved in PE remain elusive. Aberrant apoptosis and insufficient invasion of trophoblasts have been observed and are considered vital pathological features in PE. Herein, we found that miR-155 can specifically degrade the mRNA of the Hedgehog ligand sonic hedgehog (SHH), using dual luciferase reporter assays. Quantitative real-time PCR found that administering miR-155 mimics or inhibitors could significantly decrease or increase the expression of SHH in the trophoblasts, respectively. The transcription levels of miR-155 in the placenta were higher in patients with PE compared to the levels in healthy pregnant women, as shown by quantitative real-time PCR. Serum levels of miR-155 could predict the diagnosis of PE by receiver operating characteristic curve analysis and diagnosis evaluation tests. A significant increase in apoptosis was observed after administering miR-155 in HTR8/SVneo cells cultured ex vivo, accompanied by reduced proliferation. Mechanistically, transcriptional activity and expression of GLi1 were also inhibited under treatment of miR-155, and could be recovered after supplying additional recombinant human SHH to primary trophoblasts from patients, as determined by luciferase activity assays and western blotting. We further found that inhibiting miR-155 increased the production of SHH and improved the phenotype in primary trophoblasts from patients with PE. Our data show that miR-155 regulates apoptosis of trophoblasts in PE, which has potential value for predicting PE risk and might be deemed as a therapeutic target for treating PE.

No abstract

Pregnancy-associated cardiomyopathy (PAH) represents a pregnancy-associated myocardial disease that is characterized by the progression of heart failure due to marked left ventricular systolic dysfunction. Compelling evidence has highlighted the potential of angiotensin (Ang) receptor inhibitors as therapeutic targets in PAH treatment. The present study aims to elucidate the molecular mechanisms underlying Ang II receptor inhibitor LCZ696 treatment in PAH. Initially, a PAH mouse model was induced, followed by intraperitoneal injection of LCZ696. Subsequently, cardiomyocytes and fibroblasts were isolated, cultured, and treated with Ang II and LCZ696, followed by detection of the total survival rate, cardiac injury, cardiac fibrosis and apoptosis. Moreover, in order to quantify the cardiac hypertrophy and fibrosis degree of cardiac fibroblasts, the expression levels of markers of cardiac hypertrophy (ANP, βMHC and TIMP2) and markers of fibrosis (collagen I, collagen III and TGF-β) were evaluated. Furthermore, the potential effect of LCZ696 on the extracellular signal-regulated kinase (ERK) signaling pathway was examined. The acquired findings revealed that LCZ696 increased the total survival rate of PAH mice, but decreased cardiac injury, cardiac fibrosis, and apoptosis in vitro. LCZ696 attenuated cardiac injury induced by Ang II through the inhibition the expression of markers of cardiac hypertrophy, fibrosis and apoptosis by inhibiting ERK phosphorylation in vivo and in vitro. Altogether, LCZ676 could potentially alleviate cardiac remodeling in mice with PAH via blockade of the ERK signaling pathway activation. Our findings suggest that LCZ696 could be a potential target for PAH therapy.

No abstract

This study measured the total potentially available nucleoside (TPAN) content in breast milk from six different regions of China as a part of the Maternal Nutrition and Infant Investigation (MUAI) study. A total of 631 breast milk samples were collected from healthy, lactating women with singleton, full-term pregnancies between 40 and 45 days postpartum in Changchun, Chengdu, Lanzhou, Shanghai, Tianjin, and Guangzhou. TPAN and free 5′-monophosphate nucleotide (5′-MNT) contents were determined by high-performance liquid chromatography. The TPAN content of the Chinese mature milk ranged from 11.61 mg/L to 111.09 mg/L, with a median level of 43.26 mg/L. Four types of nucleotides were identified, and the median levels of cytidine monophosphate (CMP), uridine monophosphate (UMP), guanosine monophosphate (GMP), and adenosine monophosphate (AMP) were 22.84 mg/L, 9.37 mg/L, 4.86 mg/L, and 4.80 mg/L, respectively. CMP was the predominant nucleotide, accounting for 52.9% of the TPAN content, while free 5′-MNT accounted for 18.38% of the TPAN content. The distribution pattern of the TPAN content and level of the individual nucleotides were significantly different among the selected regions (p < 0.05), but the result showed no significant differences in the TPAN level in breast milk (p > 0.05). In addition, no correlation was reported between the geographic distribution and TPAN levels. This result showed that TPAN better reflects the level of total potential nucleosides in Chinese breast milk rather than 5′-MNT in free form. CMP, UMP, GMP, and AMP are the only 4 types of nucleotides reported in all detections. In addition, results revealed a large variation of TPAN levels in Chinese breast milk across six regions, so that the median value may not be the optimal fortification level of TPAN for Chinese infant populations.