High expression of Ras-related protein 1A promotes an aggressive phenotype in colorectal cancer via PTEN/FOXO3/CCND1 pathway

et al. 2020

Bioscience Reports

Background: Septic acute kidney injury is considered as a severe and frequent complication that occurs during sepsis. The present study was performed to understand the role of miR-22-3p and its underlying mechanism in sepsis-induced acute kidney injury. Methods: Rats were injected with adenovirus carrying miR-22-3p or miR-NC in the caudal vein before cecal ligation. Meanwhile, HK-2 cells were transfected with the above adenovirus following LPS stimulation. We measured the markers of renal injury (blood urea nitrogen (BUN), serum creatinine (SCR)). Histological changes in kidney tissues were examined by hematoxylin and eosin (H&E), Masson staining, periodic acid Schiff staining and TUNEL staining. The levels of IL-1β, IL-6, TNF-α and NO were determined by ELISA assay. Using TargetScan prediction and luciferase reporter assay, we predicted and validated the association between PTEN and miR-22-3p. Results: Our data showed that miR-22-3p was significantly down-regulated in a rat model of sepsis-induced acute kidney injury, in vivo and LPS-induced sepsis model in HK-2 cells, in vitro. Overexpression of miR-22-3p remarkably suppressed the inflammatory response and apoptosis via down-regulating HMGB1, p-p65, TLR4 and pro-inflammatory factors (IL-1β, IL-6, TNF-α and NO), both in vivo and in vitro. Moreover, PTEN was identified as a target of miR-22-3p. Furthermore, PTEN knockdown augmented, while overexpression reversed the suppressive role of miR-22-3p in LPS-induced inflammatory response. Conclusions: Our results showed that miR-22-3p induced protective role in sepsis-induced acute kidney injury may rely on the repression of PTEN.

Section: Introductionmentioning

confidence: 99%

MiR-22-3p suppresses sepsis-induced acute kidney injury by targeting PTEN

Wang

et al. 2020

Bioscience Reports

“…Forkhead box O3 (FOXO3) belongs to the O subclass of the forkhead family of transcription factors and is a well-established tumor suppressor 18 . FOXO3 has been shown to control various aspects of breast cancer biology 19–21 . Song et al 19 reported that restoration of FOXO3 induces apoptosis and cell cycle arrest and reverses 5-fluorouracil resistance in human breast cancer cells.…”

Section: Introductionmentioning

confidence: 99%

“…Sisci et al 20 demonstrated that overexpression of FOXO3 decreases migration, invasion, and anchorage-independent growth of estrogen receptor α-positive breast cancer cells. Multiple target genes such as CCND1 and VEGF have been proposed to mediate the anticancer activity of FOXO3 21,22 .…”

Section: Introductionmentioning

confidence: 99%

LINC01355 suppresses breast cancer growth through FOXO3-mediated transcriptional repression of CCND1

Wang

et al. 2019

Cell Death Dis

Previously, several protein-coding tumor suppressors localized at 1p36 have been reported. In the present work, we focus on functional long non-coding RNAs (lncRNAs) embedded in this locus. Small interfering RNA was used to identify lncRNA candidates with growth-suppressive activities in breast cancer. The mechanism involved was also explored. LINC01355 were downregulated in breast cancer cells relative to non-malignant breast epithelial cells. Overexpression of LINC01355 significantly inhibited proliferation, colony formation, and tumorigenesis of breast cancer cells. LINC01355 arrested breast cancer cells at the G0/G1 phase by repressing CCND1. Moreover, LINC01355 interacted with and stabilized FOXO3 protein, leading to transcriptional repression of CCND1. Importantly, LINC01355-mediated suppression of breast cancer growth was reversed by knockdown of FOXO3 or overexpression of CCND1. Clinically, LINC01355 was downregulated in breast cancer specimens and correlated with more aggressive features. There was a negative correlation between LINC01355 and CCND1 expression in breast cancer samples. LINC01355 acts as a tumor suppressor in breast cancer, which is ascribed to enhancement of FOXO3-mediated transcriptional repression of CCND1. Re-expression of LINC01355 may provide a potential therapeutic strategy to block breast cancer growth and progression.

“…It encodes a protein 403 amino acids in length and has phosphatase activity (30). It has been reported that PTEN is able to inhibit the development of tumors by antagonizing tyrosine kinase and other phosphorylases responsible for angiogenesis, cell survival and other biological processes (31). PTEN is also associated with the PI3K/protein kinase B (AKT) signaling pathway (32).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑494‑3p protects rat cardiomyocytes against septic shock via PTEN

2018

Exp Ther Med

The aim of the present study was to investigate the role of microRNA (miR)-494-3p in myocardial injury in patients with septic shock and the underlying mechanism. A total of 22 patients with sepsis and 17 patients with septic shock were included in the present study. In addition, 20 healthy subjects were recruited as the control group. Peripheral blood was collected from all subjects and a rat cardiomyocyte model of myocardial injury was constructed. Reverse transcription-quantitative polymerase chain reaction was used to measure miR-494-3p expression, while cell counting kit-8 assays were performed to assess cell proliferation. Flow cytometry was performed to investigate cell cycle distribution and apoptosis. Lactate dehydrogenase (LDH) assays were performed to measure LDH levels. ELISA was also performed to measure LDH, tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels in cell culture supernatants. Western blotting was employed to detect phosphatase and tensin homolog (PTEN) protein expression and dual luciferase reporter assays were performed to identify the interaction between miR-494-3p and PTEN mRNA. Reduced miR-494-3p expression was correlated with myocardial damage in patients with septic shock. Sera from patients with septic shock downregulated miR-494-3p expression in rat cardiomyocytes. miR-494-3p overexpression inhibited rat cardiomyocyte injury induced by treatment with sera from patients with septic shock. Furthermore, miR-494-3p overexpression reduced the synthesis and release of TNF-α and IL-6 from rat cardiomyocytes. PTEN knockdown alleviated rat cardiomyocyte injury following treatment with serum from patients with septic shock. PTEN was demonstrated to induce the release of TNF-α and IL-6 from rat cardiomyocytes treated with septic shock serum, while miR-494-3p was demonstrated to bind to the 3′-untranslated seed region of PTEN mRNA to regulate its expression. The results of the present study suggest that miR-494-3p is downregulated in the peripheral blood of patients with septic shock and is negatively correlated with myocardial injury. The present study also indicates that miR-494-3p regulates PTEN expression, inhibits sepsis-induced myocardial injury and protects the function of cardiomyocytes. The protective effect and mechanism of action of miR-494-3p indicate that it has potential for use in the clinical diagnosis and therapy of myocardial damage.