LncRNA OIP5-AS1 promotes the malignancy of pancreatic ductal adenocarcinoma via regulating miR-429/FOXD1/ERK pathway.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC), a subtype of pancreatic cancer, is a malignant tumor with unfavorable prognosis. Despite accumulating researches have made efforts on finding novel therapeutic methods for this disease, the underlying mechanism of long non-coding RNAs (lncRNAs) remains elusive. OIP5 antisense RNA 1 (OIP5-AS1) has been reported to play important role in the occurrence and development of multiple human cancers. This study was aimed at unveiling the regulatory role of OIP5-AS1 in PDAC. METHODS: RT-qPCR analysis revealed the OIP5-AS1 expression in PDAC tissues and adjacent normal ones. Kaplan-Meier method was applied to analyze the overall survival of patients with high or low level of OIP5-AS1. Gain- or loss-of function assays were performed to assess the effects of OIP5-AS1 knockdown on cell functions, including proliferation, migration and EMT process. Mechanism experiments, such as luciferase reporter and RNA pull-down assays proved the interaction between OIP5-AS1 and miR-429 as well as that between miR-429 and FOXD1. RESULTS: OIP5-AS1 was up-regulated in PDAC tissues and cell lines, and high level of OIP5-AS1 indicated poor prognosis in PDAC patients. OIP5-AS1 knockdown hindered cell proliferation, migration and epithelial-mesenchymal transition (EMT) process, while overexpression of OIP5-AS1 caused the opposite results. OIP5-AS1 activated ERK pathway through up-regulating forkhead box D1 (FOXD1) expression by sponging miR-429. Furthermore, OIP5-AS1 facilitated cell growth in vivo. CONCLUSION: OIP5-AS1 exerted oncogenic function in PDAC cells through targeting miR-429/FOXD1/ERK pathway.

LncRNA LOXL1-AS1/miR-28-5p/SEMA7A axis facilitates pancreatic cancer progression.

Pancreatic cancer (PC), one of the most aggressive and lethal human malignancies, is associated with a deplorable prognosis despite progressive therapeutic strategies. Emerging evidence manifests that miR-28-5p is involved in several cancers, and its descending expression is associated with poor prognosis. Nevertheless, the function of miR-28-5p in PC remains unclear. Thus, the underlying regulatory mechanism of miR-28-5p in PC is urgent to be clarified. In the present study, we first recognized miR-28-5p was downregulated in PC, and miR-28-5p overexpression inhibited cell proliferation and migration in PC. Then miR-28-5p was verified to act as a molecular sponge of LOXL1-AS1. Therefore, the function of LOXL1-AS1 was further explored in PC, presenting that LOXL1-AS1 suppression inhibited cell proliferation and migration. What is more, SEMA7A was found to be a target gene for miR-28-5p and was upregulated in PC. In addition, LOXL1-AS1 could positively regulate SEMA7A expression while miR-28-5p could negatively regulate SEMA7A expression. According to rescue experiments, SEMA7A overexpression partially neutralized LOXL1-AS1 silence-mediated inhibitory function on progression in PC. Taken together, all the data demonstrated that LOXL1-AS1/miR-28-5p/SEMA7A axis facilitated pancreatic cancer progression, which may be regarded as an innovative therapeutic target for PC treatment. SIGNIFICANCE OF THE STUDY: Our findings constitute the first report to delineate that lncRNA LOXL1-AS1/miR-28-5p/SEMA7A axis facilitates PC progression. According to our experimental results, we found the expression of miR-28-5p was downregulated in PC cells and miR-28-5p overexpression inhibited cell proliferation and migration in PC. LOXL1-AS1 could sponge miR-28-5p and then upregulate the expression of SEMA7A. Thus, LOXL1-AS1/miR-28-5p/SEMA7A axis facilitated PC progression. This initially proposed point might provide a novel molecular target for PC treatment.

microRNA-510-5p promotes thyroid cancer cell proliferation, migration, and invasion through suppressing SNHG15.

SNHG15 has been suggested to be correlated with clinical progression and prognosis, and function as tumor suppressive long noncoding RNA in thyroid cancer at our previous study. SNHG15 was proposed to be a potential target for miR-510-5p at LncBase Predicted database. Thus, the aim of this study was to explore the relationship between miR-510-5p and SNHG15 in thyroid cancer, and the clinical significance of miR-510-5p in patients with thyroid cancer. In our results, levels of miR-510-5p expression were increased in thyroid cancer tissues and cell lines compared with adjacent normal thyroid tissues and normal thyroid cell line, respectively. There was a statistically negative correlation between SNHG15 expression and miR-510-5p expression in thyroid cancer tissues. Moreover, miR-510-5p directly bound to SNHG15, and negatively regulated SNHG15 expression in thyroid cancer cells. Furthermore, miR-510-5p promoted thyroid cancer cell proliferation, migration, and invasion through suppressing SNHG15. Finally, high miR-510-5p expression was observed in tumor tissues with advanced clinical stage or lymph node metastasis. In conclusion, we provide evidence to support a pivotal role for miR-510-5p in regulating thyroid cancer cell proliferation, migration, and invasion.

SNHG15 functions as a tumor suppressor in thyroid cancer.

Small nucleolar RNA host gene 15 (SNHG15) has been suggested to be overexpressed, and function as an oncogenic long noncoding RNA (lncRNA) in various types of human malignancies. However, the expression status and function of SNHG15 were still unknown in thyroid cancer. In our study, we assessed the expression status and clinical value in thyroid cancer samples, and explored the effect of SNHG15 on thyroid cancer cell proliferation, migration, and invasion. In results, SNHG15 expression was downregulated in thyroid cancer tissues and cells, and correlated with age, pathology classification, clinical stage, tumor size, distant metastasis, and disease-free survival. The in vitro studies suggested SNHG15 overexpression suppressed cell proliferation, migration, and invasion in thyroid cancer. In summary, SNHG15 serves as tumor suppressive role in thyroid cancer.

Inhibition of ASAP1 Modulates the Tumor Immune Microenvironment and Suppresses Lung Cancer Metastasis via the p-STAT3 Signaling Pathway.

ADP ribosylation factor guanylate kinase 1 (ASAP1), a key protein regulating cell migration and invasion, has attracted extensive attention in oncological research in recent years. This study aims to explore the effects of ASAP1 inhibition on lung cancer metastasis and its potential mechanisms, particularly how it modulates the tumor immune microenvironment through the p-STAT3 signaling pathway. In this study, shRNA technology was employed to specifically inhibit ASAP1 expression in lung cancer cell lines A549, NCI-H1299, and PC-9. The effects of ASAP1 inhibition on lung cancer cell viability, apoptosis, migration, and invasion were evaluated using CCK-8, TUNEL apoptosis detection, and cell migration and invasion assays. Furthermore, animal experiments were conducted to assess the in vivo effects of ASAP1 inhibition on lung cancer metastasis, and immunohistochemical analysis was performed to investigate changes in immune cells in lung metastasis models, further exploring its impact on the tumor immune microenvironment. The experimental results demonstrated that ASAP1 inhibition significantly reduced lung cancer cell viability, induced apoptosis in A549, NCI-H1299, and PC-9 cells, and suppressed the migration and invasion abilities of these cells. In vivo experiments revealed that ASAP1 inhibition effectively suppressed lung cancer metastasis and altered the tumor immune microenvironment by regulating immune cells. Moreover, we found that ASAP1 inhibition could decrease tumor cell proliferation and induce tumor apoptosis in lung metastasis models by inhibiting the p-STAT3 signaling pathway. This study confirms that ASAP1 inhibition can suppress lung cancer metastasis by modulating the tumor immune microenvironment through the inhibition of the p-STAT3 signaling pathway. These findings provide new targets for lung cancer treatment and a theoretical basis for developing novel strategies against lung cancer metastasis. Future research will further explore the mechanisms of ASAP1 in lung cancer metastasis and how to optimize treatment strategies for lung cancer patients by targeting ASAP1.

Integrated supercapacitor with self-healing, arbitrary deformability and anti-freezing based on gradient interface structure from electrode to electrolyte.

Flexible supercapacitors have attracted more and more attention because of their promising applications in wearable electronics, however, it is still important to harmonize their mechanical and electrochemical properties for practical applications. In the present work, a seamless transition between polyaniline (PANI) electrode and NH4VO3_FeSO4 dual redox-mediated gel polymer electrolyte (GPE) is presented through in situ formation of gradient interface structure. Multiple physical interactions make the GPE excellent mechanical and self-healing properties. Meanwhile, double role functions of Fe2+ ions greatly relieve the traditional contradiction between mechanical and electrochemical properties of GPE. Moreover, benefiting from the structure and reversible redox reactions of VO3- and Fe2+, the integrated supercapacitor delivers an exceptional specific capacitance of 441.8 mF/cm2, a high energy density of 63.1 µWh/cm2, remarkable cyclic stability. Simultaneously, the gradient structure from PANI electrode to GPE greatly improves the electrode/electrolyte interface compatibility and ion transport, which endows the supercapacitor with stable electrochemical performance. Furthermore, the supercapacitor well-maintains the specific capacitance even at -20 °C with over 89.19 % retention after 6 cutting/healing cycles. The gradient interface structure design will promote the development of high-performance supercapacitor.

Targeting DUSP7 signaling alleviates hepatic steatosis, inflammation and oxidative stress in high fat diet (HFD)-fed mice via suppression of TAK1.

The non-alcoholic fatty liver disease (NAFLD), as a critical liver disease, is still lack of effective treatments because the molecular mechanism revealing the NAFLD pathogenesis remains unclear. Dual specific phosphatase 6 (DUSP7) shows effects on inflammatory response and is a negative feedback mechanism of the mitogen-activated protein kinase (MAPK) superfamily, which are critical factors in regulating NAFLD progression. However, the effects of DUSP7 on hepatic steatosis are still not fully understood. Here, we found that DUSP7 functioned as a negative regulator of NAFLD and in various metabolic disorders. DUSP7 expression was markedly reduced in liver samples from patients with simple hepatic steatosis or non-alcoholic steatohepatitis (NASH), as well as in liver tissues from high fat diet (HFD)-challenged mice or genetically obese (ob/ob) mice. DUSP7 knockout markedly accelerated insulin resistance, glucose intolerance, liver dysfunction, fibrosis and hepatic steatosis in HFD-fed mice. In addition, inflammatory response was significantly exacerbated in HFD-challenged mice with DUSP7 deletion, which was associated with the elevated activation of nuclear factor-κB (NF-κB) and MAPKs signaling pathways. Moreover, oxidative stress was detected in liver of HFD-induced mice, and this phenomenon was aggravated in mice with DUSP7 knockout. Importantly, we demonstrated that DUSP7 physically interacted with transforming growth factor ß (TGF-ß)-activated kinase (TAK1). DUSP7 deletion considerably promoted the activation of TAK1 in mice after HFD feeding, contributing to the lipid deposition, inflammatory response and reactive oxygen species (ROS) production. Taken together, DUSP7 might function as a protective factor against NAFLD development and metabolic disorder through alleviating dyslipidemia, inflammation and oxidative stress by directly interacting with TAK1 in hepatocytes, which was involved in the suppression of fibrosis. Thus, we may provide an effective strategy for the treatment of hepatic steatosis via targeting DUSP7.

Overexpression of microRNA-519d-3p suppressed the growth of pancreatic cancer cells by inhibiting ribosomal protein S15A-mediated Wnt/ß-catenin signaling.

Ribosomal protein S15A (RPS15A) has emerged as a novel oncogene of various human cancers. However, whether RPS15A is involved in pancreatic cancer remains unclear. In this study, we aimed to investigate the potential relevance of RPS15A in pancreatic cancer and elucidate the underlying regulatory mechanism. We found that RPS15A expression was significantly up-regulated in pancreatic cancer cell lines. RPS15A knockdown resulted in a decrease of cell proliferation and colony formation, and induced cell cycle arrest in G0/G1 phases of pancreatic cancer cells in vitro. In addition, RPS15A knockdown down-regulated ß-catenin expression and blocked the activation of Wnt signaling. Notably, RPS15A was identified as a target gene of microRNA-519d-3p (miR-519d-3p), a tumor suppressive miRNA. Further data showed that miR-519d-3p negatively regulated RPS15A expression in pancreatic cancer cells. Moreover, miR-591d-3p expression was significantly decreased in pancreatic cancer cell lines and tissues and was inversely correlated with RPS15A expression. The overexpression of miR-519d-3p significantly inhibited the proliferation and Wnt/ß-catenin signaling in pancreatic cancer cells, mimicking the similar effect of RPS15A knockdown. However, restoration of RPS15A expression partially reversed the antitumor effect of miR-519d-3p. Taken together, our results demonstrate that RPS15A knockdown or RPS15A inhibition by miR-519d-3p suppresses the growth of pancreatic cancer cells associated with the inhibition of Wnt/ß-catenin signaling. Our study suggests that the miR-519d-3p/RPS15A/Wnt/ß-catenin regulation axis plays an important role in the progression of pancreatic cancer and may serve as potential targets for treatment of pancreatic cancer.

Down-regulation of fractalkine inhibits the in vitro and in vivo angiogenesis of the hepatocellular carcinoma HepG2 cells.

There is increasing evidence that hepatocellular carcinoma (HCC) is inherently associated with the inflammatory process and the up-regulation of cytokines. Our study aimed at elucidating the role of the cytokine fractalkine in the process of HCC carcinogenesis. Expression of fractalkine in hepatocellular carcinoma cell line HepG2 was knocked-down by RNAi. Conditioned media (CMs) from HepG2 was used in angiogenesis assays both in vitro and in vivo. Compared with CMs from mock transfection and negative shRNA treated HepG2, CMs from fractalkine shRNA treated HepG2 highly suppressed the migration, proliferation, and differentiation of human umbilical vein endothelial cells. The results suggest that fractalkine may play a key role in the mechanism of angiogenesis and carcinogenesis of HCC.