Melatonin alleviates insulin resistance through the PI3K/AKT signaling pathway in ovary granulosa cells of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine gynecological disorder. Insulin resistance (IR) is a major cause of PCOS. Melatonin, a critical endogenous hormone, has beneficial effects on the female reproductive system. This study aims to investigate the molecular effect of melatonin on IR in human ovarian granulosa cells (GCs). Hormone levels of the subjects were determined through clinical examination. The expression levels of insulin receptor substrate (IRS)-1 and glucose transporter (GLUT4) in GCs from PCOS patients and a human granulosa cell line (SVOG) were examined using qRT-PCR and western blot. The IR cell model was established by inducing SVOG cells with palmitic acid (PA). IR was detected in GCs of PCOS patients and SVOG by measuring glucose content and glucose uptake. Cell viability and apoptosis levels were detected by CCK-8 assay and flow cytometry. PI3K/Akt pathway expression in SVOG was assessed by western blot. PCOS patients had higher levels of luteinizing hormone (LH), testosterone, and LH/follicle-stimulating hormone. PA decreased cell viability, promoted apoptosis, and reduced glucose uptake in SVOG cells. IRS-1 and GLUT4 mRNA and protein expression was downregulated, and glucose uptake capacity was reduced in PCOS GCs and SVOG cells. Melatonin significantly upregulated IRS-1 and GLUT4 expression, downregulated p-IRS-1 (Ser307), and improved glucose uptake in PCOS patients' GCs and SVOG cells. PA decreased PI3K and Akt phosphorylation, whereas melatonin increased p-PI3K and p-Akt levels. Melatonin can reduce IR in GCs and PA-induced SVOG cells via the PI3K/Akt signaling pathway, providing more evidence for treating polycystic ovary syndrome.

Long Noncoding RNA FEZF1-AS1 Promotes Proliferation and Inhibits Apoptosis in Ovarian Cancer by Activation of JAK-STAT3 Pathway.

BACKGROUND Long noncoding RNAs (lncRNAs) have been acknowledged as important regulators in human cancers, including ovarian cancer. Several reports identified lncRNA FEZF1-AS1 as an oncogene in gastric cancer, colorectal carcinoma, and non-small cell lung cancer (NSCLC). However, the function of FEZF1-AS1 in ovarian cancer remains largely unknown. This study was aimed to investigate the role of FEZF1-AS1 in ovarian cancer. MATERIAL AND METHODS FEZF1-AS1 expression levels in pairs of ovarian cancer tissues and adjacent normal tissues were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier curve analysis was used to determine the correlation between FEZF1-AS1 expression and prognosis in ovarian cancer patients. The effects of FEZF1-AS1 knockdown on ovarian cancer cell proliferation, cell-cycle, and apoptosis were analyzed by Cell Counting Kit-8 (CCK8) and Fluorescence activated Cell Sorting (FACS) assays. Western blot was utilized to assess the effect of FEZF1-AS1 on the activation of JAK-STAT3 pathway. RESULTS FEZF1-AS1 was overexpressed in ovarian cancer tissues compared to adjacent normal tissues. Consistently, FEZF1-AS1 expression was also upregulated in ovarian cancer cell lines compared with normal cell line. Furthermore, higher expression of FEZF1-AS1 in ovarian cancer patients contributed to poorer prognosis. FEZF1-AS1 knockdown significantly suppressed the proliferation and promoted apoptosis in ovarian cancer cells. In mechanism, FEZF1-AS1 regulated activation of JAK-STAT3 signaling pathway by modulating STAT3 phosphorylation. Knockdown of FEZF1-AS1 significantly impaired the phosphorylation of STAT3. CONCLUSIONS Our study demonstrated that FEZF1-AS1 exerted an oncogenic role in ovarian cancer via modulating JAK-STAT3 pathway.