miR-141-3p inhibits fibroblast proliferation and migration by targeting GAB1 in keloids.

Keloids are benign dermal fibroproliferative tumors that develop as a result of several dysregulated processes. Emerging evidence has revealed that miRNAs contribute to keloid formation. However, the molecular mechanisms of keloid pathogenesis remain unclear. In our study, we found that miR-141-3p in keloid tissues and keloid fibroblasts was significantly decreased compared with the levels in normal tissues and normal skin fibroblasts, respectively. miR-141-3p overexpression resulted in significantly decreased proliferation and migration and the promotion of apoptosis in keloid fibroblasts, whereas miR-141-3p knockdown in keloid fibroblasts yielded the opposite results. Growth factor receptor binding 2-associated binding protein 1 (GAB1) was identified and confirmed as a direct target of miR-141-3p. The expression of GAB1 was up-regulated in keloid tissues, and the restoration of GAB1 partially reversed the inhibitory effects of miR-141-3p on the proliferation and migration of keloid fibroblasts. All data suggested that miR-141-3p decreased the proliferation and migration of keloid fibroblasts by repressing GAB1 expression, providing a useful target for keloid management.

MiR-181a Targets PHLPP2 to Augment AKT Signaling and Regulate Proliferation and Apoptosis in Human Keloid Fibroblasts.

BACKGROUND/AIMS: Keloids are fibrous overgrowths induced by cutaneous injury. MicroRNAs (miRNAs) have recently emerged as post-transcriptional gene repressors and participants in a diverse array of pathophysiological processes leading to skin disease. The purpose of the current study was to explore the precise functions of miR-181a in human keloid development and the underlying mechanisms. METHODS: A miRNA microarray analysis was performed to compare expression profiles between keloid and normal skin tissues. Quantitative real-time PCR was conducted to estimate miR-181a expression. Cell proliferation was determined using the cell counting kit-8 (CCK-8) and 5-ethynyl-2-deoxyuridine (EdU) assays, and cell cycle and apoptosis were detected with flow cytometry. Direct targets of miR-181a were identified using the luciferase reporter assay. RESULTS: miR-181a was significantly upregulated in human keloid tissues and fibroblasts, compared with their control counterparts. Overexpression of miR-181a enhanced keloid fibroblast DNA synthesis and proliferation and inhibited apoptosis, whereas miR-181a suppression triggered the opposite effects. Moreover, miR-181a suppressed the expression of PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2) through direct interactions with its 3'UTR region and subsequently enhanced AKT activation. Overexpression of PHLPP2 without its 3'UTR attenuated the effects of miR-181a on cell proliferation and apoptosis in keloid fibroblast cells. Furthermore, miR-181a mimics increased normal skin fibroblast proliferation. CONCLUSIONS: Our results highlight a novel pathway mediated by miR-181a, which may be effectively used as a therapeutic target for treatment of keloids.

miR-542-3p suppresses invasion and metastasis by targeting the proto-oncogene serine/threonine protein kinase, PIM1, in melanoma.

Aberrant microRNAs (miRNAs) contribute to metastasis of various cancer types, including melanoma. miR-542-3p has been characterized as a tumor suppressor in several cancers. However, the exact expression patterns of miR-542-3p and the precise molecular mechanisms underlying its role in melanoma require further exploration. In the current study, we demonstrated that miR-542-3p is significantly downregulated in melanoma cell lines and clinical specimens. Exogenous expression of miR-542-3p resulted in marked inhibition of melanoma cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and lung metastasis in vivo. The proto-oncogene serine/threonine protein kinase, PIM1, was identified as a direct target of miR-542-3p using luciferase reporter assay, qRT-PCR and western blot analyses. Overexpression of PIM1 partially rescued miR-542-3p-mediated suppression of cell migration, invasion and EMT. Our results collectively indicate that miR-542-3p serves as a metastasis suppressor in melanoma, supporting its utility as a promising therapeutic candidate.

Effects of angle and accumulative irradiation on ability of antioxidation and the antioxidase activity on rats / 中华放射医学与防护杂志

Objective To compare the changes in nitric oxide (NO), total ability of anti-oxidize antioxidase, superoxide dismutase (SOD), glutathion peroxidase (GSH-PX), catalase (CAT) and maleic dialdehyde(MDA) in rats after single and accumulative 60Co γ-irradiation . Methods 48 rats were randomly divided into two groups of single and accumulative irradiation. Each group was irradiated by 60Co gamma-rays. The total irradiation doses were 0.4, 0.8, 1.6, 3.2 and 6.4 Gy, respectively in each group. The NO, total ability of anti-oxidize antioxidaze, SOD, GSH-PX, CAT and MDA in serum were measured at day 1 after last irradiation. Results Compared with the single irradiation group, the NO (52.6-117.9 μmol/ml), total ability of anti-oxidize antioxidaze (3.3-26.2 U/ml), the antioxidase activity of the SOD (26.3-167.5 U/ml), GSH-PX (740.8-2462.4 U/ml), CAT (3.3-29.4 U/ml) and the content of MDA(29.3-155.1 nmol/ml) of mt serum in accumulative irradiation group were increased after irradiation, which was related with the accumulative irradiation dose. For instance, total ability of anti-oxidize antioxidase (26.2 U/ml), antioxidase activity of the SOD (167.5 U/ml) and CAT (29.4 U/ml) in 0.4 Gy group of accumulative irradiation were significandy increased when compared with those of control group. However, the content of MDA in accumulative irradiation group was obviously higher than that in single radiation group when the irradiation doses delivered over 3.2 Gy, which might be correlated with higher antioxidase activity. Conclusions Low dose of accumulative gamma-rays irradiation can induce the stimulative effect of antioxidase activity. However, higher dose of accumulative gamma-rays irradiation can damage the activity of antioxidase.