A novel long non-coding RNA TTN-AS1/microRNA-589-5p/FOXP1 positive feedback loop increases the proliferation, migration and invasion of pancreatic cancer cell lines.

Numerous reports have found that long non-coding (lnc) RNAs were associated with pancreatic cancer (PC) initiation and development. The lncRNA titin antisense RNA 1 (TTN-AS1) was identified as a tumor promoter in certain types of cancer; however, its role and mechanism in PC remain unclear. The aim of the present study was to investigate the role of TTN-AS1 in PC and elucidate the underlying mechanism. Reverse transcription-quantitative PCR analysis was performed to examine the mRNA expression level of TTN-AS1, microRNA(miR)-589-5p and forkhead box protein 1 (FOXP1). Knockdown experiments were performed to examine the effect of TTN-AS1 on PC cell proliferation, migration and invasion. Luciferase reporter assays validated the binding of miR-589-5p to TTN-AS1 and FOXP1. Chromatin immunoprecipitation and luciferase reporter assays confirmed the binding ability of FOXP1 to the TTN-AS1 promoter. As a result, TTN-AS1 and FOXP1 were found to be upregulated in PC cell lines and tissues, while miR-589-5p was expressed at low levels. Knockdown experiments indicated the suppressive effect of TTN-AS1 knockdown on cell proliferation, migration and invasion in PC cell lines. Further mechanistic research uncovered that TTN-AS1 functioned as a molecular sponge for miR-589-5p and its mRNA expression level in PC tissues was inversely associated with that of miR-589-5p. Furthermore, miR-589-5p was confirmed to target FOXP1. Of note, it was discovered that FOXP1 transcriptionally activated TTN-AS1 mRNA expression level. Taken together, the findings of the present study demonstrated that the new TTN-AS1/miR-589-5p/FOXP1 feedback loop may play an important role in PC.

Hypoxic postconditioning-induced neuroprotection increases neuronal autophagy via activation of the SIRT1/FoxO1 signaling pathway in rats with global cerebral ischemia.

Hypoxic postconditioning (HPC) has been reported to be a beneficial and promising treatment for global cerebral ischemia (GCI). However, its neuroprotective mechanism remains unclear. The aim of the present study was to determine whether the protective effects of HPC in a rat model of GCI were due to the upregulation of autophagy via the silent information regulator transcript-1 (SIRT1)/Forkhead box protein 1 (FoxO1) pathway. Morris water maze test revealed that HPC attenuated cognitive damage in GCI rats. HPC also significantly increased the levels of the autophagy-related protein LC3-II, SIRT1 and FoxO1 compared with those in the GCI group. However, the HPC-induced LC3-II upregulation was blocked by the SIRT1 inhibitor EX527. These results suggested that the beneficial effects of HPC on GCI rats were due to the upregulation of ischemiainduced autophagy and involved the SIRT1/FoxO1 signaling pathway.

FOXP1 syndrome: a review of the literature and practice parameters for medical assessment and monitoring.

FOXP1 syndrome is a neurodevelopmental disorder caused by mutations or deletions that disrupt the forkhead box protein 1 (FOXP1) gene, which encodes a transcription factor important for the early development of many organ systems, including the brain. Numerous clinical studies have elucidated the role of FOXP1 in neurodevelopment and have characterized a phenotype. FOXP1 syndrome is associated with intellectual disability, language deficits, autism spectrum disorder, hypotonia, and congenital anomalies, including mild dysmorphic features, and brain, cardiac, and urogenital abnormalities. Here, we present a review of human studies summarizing the clinical features of individuals with FOXP1 syndrome and enlist a multidisciplinary group of clinicians (pediatrics, genetics, psychiatry, neurology, cardiology, endocrinology, nephrology, and psychology) to provide recommendations for the assessment of FOXP1 syndrome.

MicroRNA-152 inhibits ovarian cancer cell proliferation and migration and may infer improved outcomes in ovarian cancer through targeting FOXP1.

microRNA (miR) are a class of endogenous small non-coding RNA that are aberrantly expressed and are critical in tumorigenesis. Amongst them, miR-152 was reported to be dysregulated in epithelial ovarian cancer (EOC). However, the function and mechanism of miR-152 is not well understood. In the present study, total RNA was extracted from 58 ovarian epithelial carcinoma tissue samples and adjacent non-tumor tissues and measured by reverse transcription-quantitative polymerase chain reaction. The observations of the present study revealed that the expression of miR-152 was significantly downregulated in EOC specimens, as well as three ovarian cancer (OC) cell lines. The higher expression of miR-152 indicated a better overall survival rate in patients with EOC. Following miR-152 mimic transfection into SKOV3 or OVCAR3 cells, MTT assay revealed that cell proliferation was significantly inhibited (P<0.05). Although miR-152 had no effect on SKOV3 cell migration, miR-152 inhibited OVCAR3 cell migration. Bioinformatics analyses and luciferase reporter assays demonstrated that miR-152 targeted the 3'-untranslated region (3'-UTR) of the forkhead box protein 1 (FOXP1). Furthermore, introducing FOXP1 without the 3'-UTR abrogated the effect of miR-152-induced proliferation and migration alteration, respectively. In addition, the expression level of FOXP1 was higher in the EOC tumor tissues and cell lines. Additionally, the level of miR-152 and FOXP1 was inversely correlated in grade 3 and 4 ovarian tumor tissues. Altogether, these observations indicated that miR-152 may be involved in the inhibition of OC through repression of FOXP1. In the future, miR-152 and FOXP1 may act as novel biomarkers for early detection of EOC or therapeutic targets.

The possible role of diet in the pathogenesis of adult female acne.

Acne in adults is a chronic, increasingly common disease, especially among women. It differs in pathogenesis and clinical presentation from adolescent acne. Acne in adults is associated with Western diet, defined as high consumption of milk, high glycemic load and high calorie intake. Metabolic signals of this diet result in a significant increase in insulin/insulin growth factor 1 serum level and consequently in the molecular interplay of mammalian target of rapamycin complex 1 kinase (mTORC1)/forkhead box protein 1 (FoxO1) mediated nutrient signaling, leading to increased proliferation of keratinocytes, increased lipogenesis and sebum production and finally to aggravation of acne.

FOXP1 and SPINK1 reflect the risk of cirrhosis progression to HCC with HBV infection.

BACKGROUND: Hepatocellular carcinoma (HCC) deriving from cirrhosis with HBV infection harbors higher morbidity and poor prognosis. The diagnosis of HCC at its early stage is essential for improving the effect of treatment and survival rate of patients. METHOD: Affymetrix GeneChip was practiced to establish gene expression profile and significance analysis of microarray (SAM) as well as prediction analysis of microarray (PAM) was utilized to screen candidate marker genes in tissue of carcinoma and para-cancerous with cirrhosis from 15 hepatitis B virus (HBV) related HCC patients. RESULT: Total 497 differential genes were selected by microarray (fold change >2; P value<0.01). Then 162 significant genes were determined by SAM (fold change -1.46 to 1.28). A number of 8-genes showing "poor risk signature" was validated with threshold of 6.2, which was associated with cirrhosis progressing to HCC. Only 3 down-regulated and 2 up-regulated predictor genes had statistical difference in HCC and cirrhosis groups by RT-PCR (P value<0.01). Forkhead box protein 1 (FOXP1) and serine protease inhibitor Kazal-type 1 (SPINK1) proteins were found significantly increased in carcinoma tissues than para-cancerous cirrhotic tissues by IH and WB. CONCLUSION: Over-expression of FOXP1 and SPINK1 may participate in the carcinogenesis of HBV related cirrhosis. They could use as potential biomarkers for diagnosing early HCC.