Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “progress”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

WIP promotes in-vitro invasion ability, anchorage independent growth and EMT progression of A549 lung adenocarcinoma cells by regulating RhoA levels

Cancer cell migration and invasion involves actin cytoskeleton reorganization, which is regulated by the WASP (Wiskott Aldrich Syndrome Protein) family of proteins such as WASP, N-WASP (Neural-WASP) and WASP interacting protein (WIP). In this study, we found that the expression of WIP was significantly upregulated in metastatic A5-RT3 cells compared to its parental non-tumorigenic HaCaT cells. Using A549 human lung adenocarcinoma cell line as the model system, we found that WIP regulates cell invasion, proliferation and anchorage-independent growth. Expression of WIP was enhanced during TGF-β1 induced epithelial-mesenchymal transition (EMT) and overexpression of WIP accelerated EMT while knocking down WIP attenuated EMT associated morphological changes. Knocking down WIP expression in A549 cells significantly reduced RhoA levels and WIP was found to interact with RhoA suggesting that WIP might be executing its function by regulating RhoA. Acquisition of invasive, proliferative properties and anoikis resistance is the central step in metastasis indicating a novel function of WIP in cancer progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

MicroRNA-144-3p suppresses gastric cancer progression by inhibiting epithelial-to-mesenchymal transition through targeting PBX3

MicroRNAs are aberrantly expressed in a wide variety of human cancers. The present study aims to elucidate the effects and molecular mechanisms of miR-144-3p that underlie gastric cancer (GC) development. It was observed that miR-144-3p expression was significantly decreased in GC tissues compared to that in paired non-tumor tissues; moreover, its expression was lower in tissues of advanced stage and larger tumor size, as well as in lymph node metastasis tissues compared to that in control groups. miR-144-3p expression was associated with depth of invasion (P = 0.030), tumor size (P = 0.047), lymph node metastasis (P = 0.047), and TNM stage (P = 0.048). Additionally, miR-144-3p significantly inhibited proliferation, migration, and invasion in GC cells. It also reduced F-actin expression and suppressed epithelial-to-mesenchymal transition (EMT) in GC cells. Furthermore, pre-leukemia transcription factor 3 (PBX3) was a direct target gene of miR-144-3p. PBX3 was overexpressed in GC tissues and promoted EMT in GC cells. The effects of miR-144-3p mimics or inhibitors on cell migration, invasion, and proliferation were reversed by PBX3 overexpression or downregulation respectively. These results suggest that miR-144-3p suppresses GC progression by inhibiting EMT through targeting PBX3. - Highlights: • miR-144-3p is downregulated in gastric cancer tissues and associated with malignant clinical factors. • miR-144-3p inhibits proliferation, migration, and invasion in gastric cancer cells. • PBX3 is a direct target of miR-144-3p and promotes EMT in gastric cancer. • miR-144-3p suppresses EMT in gastric cancer by regulating PBX3.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

USP5 promotes tumorigenesis and progression of pancreatic cancer by stabilizing FoxM1 protein

Increased ubiquitin-specific protease 5 (USP5) has been associated with tumorigenesis of malignancy including glioblastoma, melanoma and hepatocellular carcinoma. However, the role of USP5 in tumorigenesis of pancreatic ductal adenocarcinoma (PDAC) has not been studied yet. In this study, we demonstrated that USP5 was significantly upregulated in a panel of PDAC cell lines and correlated with FoxM1 protein expression. USP5 knockdown inhibited proliferation of PANC-1 and SW1990, two PDAC cell lines. In the mouse xenografted pancreatic tumor model, suppression of USP5 significantly decreased tumor growth, correlated with down regulation of FoxM1. Additionally, we found that overexpression of USP5 stabilized the FoxM1 protein in PDAC cells. Overexpression of USP5 extended the half-life of FoxM1. Knockdown of USP5 in PANC-1 cells decreased FoxM1 protein level while the proteasome inhibitor MG-132 treatment restored FoxM1 expression. We also found that endogenous USP5 was coimmunoprecipitated with an endogenous FoxM1 from PANC-1 cells while FoxM1 was also coimmunoprecipitated with USP5. Furthermore, we also confirmed that USP5 regulated proliferation of PDAC via FoxM1 by rescuing the inhibitory effect of USP5 knockdown with ectopic expression of FoxM1 in USP5-depleted cells. Taken together, our study demonstrates that USP5 plays a critical role in tumorigenesis and progression of pancreatic cancer by stabilizing FoxM1 protein, and provides a rationale for USP5 being a potential therapeutic approach against PDAC. - Highlights: • USP5 is upregulated in pancreatic ductal adenocarcinoma cells. • USP5 promotes tumorigenesis of pancreatic cancer. • USP5 stabilizes FoxM1 protein.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Upregulation of PAG1/Cbp contributes to adipose-derived mesenchymal stem cells promoted tumor progression and chemoresistance in breast cancer

C-terminal Src kinase (Csk)-binding protein (Cbp) is a ubiquitously expressed transmembrane adaptor protein which regulating Src family kinase (SFK) activities. Although SFKs are well known for their involvement in breast cancer, the function of Cbp in breast carcinogenesis upon the adipose-tumor microenvironment has not been investigated. Here, we reported that adipose-derived mesenchymal stem cells (ASCs) induced increased expression of Cbp accompanied by enhanced cell proliferation and chemotherapy resistance in breast cancer cell MCF-7/ADR. Depletion of Cbp in breast cancer cell by RNA interference led to remarkable inhibition of cell proliferation, invasion as well as synergy with adriamycin hydrochloride to suppress the tumor growth. Furthermore, silencing of Cbp concomitantly inhibited the expression of phosphoryl of Src, AKT and mTOR signals. Our study highlights the underlying mechanism of cross interaction between ASCs and breast cancer cells, and indicates that PAG1/Cbp in breast cancer cell may modulate tumor progression and acquired chemoresistance in the ASCs-associated breast cancer microenvironment through Src and AKT/mTOR pathways.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

NFκB mediated elevation of KCNJ11 promotes tumor progression of hepatocellular carcinoma through interaction of lactate dehydrogenase A

Highlights: • Upregulated KCNJ11 predicts a poor prognosis and is regulated by NFκB signaling in HCC. • KCNJ11 knockdown suppresses HCC cell proliferation, apoptosis-resistance, and migration in vitro. • KCNJ11 interacts with LDHA. • LDHA partially mediated the oncogenic roles of KCNJ11 in HCC. It has been well documented that changes in ion fluxes across cellular membranes is fundamental in maintaining cellular homeostasis. Dysregulation and/or malfunction of ion channels are critical events in the pathogenesis of diverse diseases, including cancers. In this study, we focused on the study of K{sup +} channels in hepatocellular carcinoma (HCC). By data mining TCGA cohort, the expression of 27 K{sup +} channels was investigated and KCNJ11 was identified as a key dysregulated K{sup +} channels in HCC. KCNJ11 was differentially expressed in HCC and predicted a poor prognosis in HCC patients. Inhibition of NFκB signaling suppressed KCNJ11 expression in HCC cells. Knockdown of KCNJ11 expression inhibited cell proliferation, promoted cell apoptosis, and reduced cell invasive capacity. Mechanistically, we found that KCNJ11 promotes tumor progression through interaction with LDHA and enhancing its enzymatic activity. Pharmacological inhibition of LDHA largely compromised the oncogenic function of KCNJ11 in cell proliferation, cell apoptosis, and cell invasion. Collectively, our data, as a proof of principle, demonstrate that KCNJ11 acts as an oncogene in HCC though forming a complex with LDHA and suggest that targeting KCNJ11 can be developed as a candidate tool to dampen HCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Inhibition of CIP2A attenuates tumor progression by inducing cell cycle arrest and promoting cellular senescence in hepatocellular carcinoma

Highlights: • High expression level of CIP2A was frequently observed in hepatocellular carcinoma (HCC). • CIP2A expression level was associated with unfavorable overall and recurrence-free survival in HCC patients. • Inhibition of CIP2A attenuated HCC progression via inducing cell cycle arrest and promoting cellular senescence. CIP2A is a recent identified oncogene that inhibits protein phosphatase 2A (PP2A) and stabilizes c-Myc in cancer cells. To investigate the potential oncogenic role and prognostic value of CIP2A, we comprehensively analyzed the CIP2A expression levels in pan-cancer and observed high expression level of CIP2A in majority cancer types, including hepatocellular carcinoma (HCC). Based on a validation cohort including 60 HCC and 20 non-tumorous tissue samples, we further confirmed the high mRNA and protein expression levels of CIP2A in HCC, and found high CIP2A mRNA expression level was associated with unfavorable overall and recurrence-free survival in patients with HCC. Mechanistic investigations revealed that inhibition of CIP2A significantly attenuated cellular proliferation in vitro and tumourigenicity in vivo. Bioinformatic analysis suggested that CIP2A might be involved in regulating cell cycle. Our experimental data further confirmed CIP2A knockdown induced cell cycle arrest at G1 phase. We found accumulated cellular senescence in HCC cells with CIP2A knockdown, companying expression changes of senescence associated proteins (p21, CDK2, CDK4, cyclin D1, MCM7 and FoxM1). Mechanistically, CIP2A knockdown repressed FoxM1 expression and induced FoxM1 dephosphorylation. Moreover, inhibition of PP2A by phosphatase inhibitor rescued the repression of FoxM1. Taken together, our results showed that CIP2A was highly expressed in HCC. Inhibition of CIP2A induced cell cycle arrest and promoted cellular senescence via repressing FoxM1 transcriptional activity, suggesting a potential anti-cancer target for patients with HCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Co-administration of APD668, a G protein-coupled receptor 119 agonist and linagliptin, a DPPIV inhibitor, prevents progression of steatohepatitis in mice fed on a high trans-fat diet

Highlights: • GPR119 a novel therapeutic target for the treatment of dyslipidemia and NASH. • APD668, a GPR119 receptor agonist ameliorated hepatic steatosis in NASH mice. • Co-administration of APD668 and linagliptin resulted in increased GLP-1 levels. • Combination treatment demonstrated enhanced effects in NASH mice. Non-Alcoholic SteatoHepatitis (NASH) is the more severe form of Non-Alcoholic Fatty Liver Disease (NAFLD) and is characterized by the presence of hepatic steatosis, oxidative stress, inflammation, hepatocyte injury with or without fibrosis. Recently, GPR119 receptor has emerged as a novel therapeutic target for the treatment of dyslipidemia and non-alcoholic steatohepatitis. In the present study, we investigated the effect of APD668, a GPR119 agonist alone or in combination with linagliptin, a DPPIV inhibitor on the progression of steatohepatitis in mice fed on a high trans-fat diet. In this study, monotherapy with either APD668 or linagliptin caused a reduction in the levels of ALT, AST, glucose, cholesterol and epididymal fat mass but the effect was more pronounced upon treatment with combination of both drugs. On the other hand, combined treatment of APD668 with linagliptin demonstrated a non-significant additive effect in reduction of hepatic triglyceride (−78%) and cholesterol (−56%) compared to monotherapy groups. Moreover, co-administration of APD668 and linagliptin resulted in enhanced levels of active GLP-1 with additional benefit of significant synergistic decrease in body weight gain (−19%) in mice. We speculated that the enhanced effect observed with the combination treatment could be due to either 1) direct activation of GPR119 receptors present in liver and intestine or 2) enhanced active GLP-1 levels or 3) decreased degradation of GLP-1 in-vivo through DPPIV inhibition. Therefore, these findings clearly suggest that GPR119 receptor agonists in combination with DPPIV inhibitors may represent a promising therapeutic strategy for the treatment of non-alcoholic steatohepatitis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

TINCR facilitates non-small cell lung cancer progression through BRAF-activated MAPK pathway

Highlights: • TINCR facilitates NSCLC. • TINCR interacts with BRAF. • TINCR activates MAPK by BRAF. Long non-coding RNAs are critically involved in oncogenesis in various cancer types. Here we reported a novel lncRNA signature correlated with progression of non-small cell lung cancer (NSCLC). In particular, we identified elevated expression of terminal differentiation-induced noncoding RNA (TINCR) in human NSCLC samples, which were associated with enhanced migration, viability in NSCLC cells in vitro. Higher TINCR level was also correlated with poor survival. Furthermore, TINCR increased xenograft tumor growth in vivo mouse models. Mechanistic study demonstrated that TINCR can interact with BRAF to facilitate its kinase activity, thereby leading to activation of oncogenic mitogen-activated protein kinase (MAPK) pathway. These results suggested that TINCR upregulation may signal through the MAPK pathway to promote NSCLC tumorigenesis. Therefore, TINCR may serve as a potential prognostic marker and therapeutic target for NSCLC patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

miR-196b is a prognostic factor of human laryngeal squamous cell carcinoma and promotes tumor progression by targeting SOCS2

Highlights: • Aberrant expression of miR-196b and SOCS2 were found in LSCC samples. • MiR-196b can directly inhibit SOCS2 expression in LSCC cells in vitro. • MiR-196b promotes LSCC cells proliferation and invasion by inhibiting SOCS2. • MiR-196b/SOCS2 pathway are correlated with LSCC progression in clinic. • MiR-196b serves as an effective prognostic factor of LSCC. Laryngeal squamous cell carcinoma (LSCC) has the second highest incidence among the head and neck malignancies. Additionally, the incidence of LSCCs has been recently increasing. Therefore, understanding the mechanisms of LSCC tumorigenesis and identifying novel biomarkers to accurately predict and improve the prognosis of patients with LSCC is extremely important.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

m6A demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression

Highlights: • The prognostic value of m{sup 6}A methyltransferase and demethylase in lung cancer. • Differentially expressed FTO accounts for the aberrant m{sup 6}A modification in LUSC. • FTO acts as an oncogene in LUSC. • MZF1 mediates FTO regulation in LUSC. N{sup 6}-Methyladenosine (m{sup 6}A) represents the most prevalent internal modification in mammalian mRNAs. Emerging evidences suggest that m{sup 6}A modification is profoundly implicated in many biological processes, including cancer development. However, limited knowledge is available about the functional importance of m{sup 6}A in lung cancer. In this study, by data mining The Cancer Genome Atlas (TCGA) database, we first identified fat mass- and obesity-associated protein (FTO) as a prognostic factor for lung squamous cell carcinoma (LUSC). Then we showed that FTO, but not other m{sup 6}A modification genes including METTL3, METTL14 and ALKBH5, was the major dysregulated factor responsible for aberrant m{sup 6}A modification in LUSC. Loss-of-function studies suggested that FTO knockdown effectively inhibited cell proliferation and invasion, while promoted cell apoptosis of L78 and NCI-H520 cells. Furthermore, overexpression of FTO, but not its mutant form, facilitated the malignant phenotypes of CHLH-1 cells. Mechanistically, FTO enhanced MZF1 expression by reducing m{sup 6}A levels and mRNA stability in MZF1 mRNA transcript, leading to oncogenic functions. Taken together, our study demonstrates the functional importance of FTO in the tumor progression of LUSC and provides a potential therapeutic target for LUSC treatment.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

RHCG suppresses cervical cancer progression through inhibiting migration and inducing apoptosis regulated by TGF-β1

Highlights: • Expression of RHCG is associated with human cervical cancer development. • RHCG regulates migration and apoptosis in human cervical cancer cell lines. • RHCG modulates TGF-β1 expressions to reduce migration and induce apoptosis in human cervical cancer cell lines. Cervical cancer is the second commonest cancer among women in the worldwide, and the majority cause of death in various countries, highlighting the importance of investigating new therapeutic targets. Rh family, C glycoprotein (RHCG) belongs to the Rhesus (Rh) family and was first identified as Rh blood group antigens. It has been confirmed to function in cancer progression, including prostate cancer and esophageal squamous cell carcinoma. However, its role in cervical cancer has never been explored. The present study indicated that RHCG was down-regulated in cervical cancers compared to that in normal cervical tissues, and further decreased in cervical cancer cell lines. Functionally, RHCG overexpression reduced cervical cancer cell proliferation and migration, as evidenced by the decreased transforming growth factor (TGF)-β1, matrix metalloproteinase (MMP)-2 and MMP-9 expressions in cancer cells; however, an opposite effect was observed when RHCG was knocked down. Further, increase of RHCG markedly induced apoptosis in cervical cancer cells by improving the cleavage of Caspase-3 and poly (ADP-Ribose) polymerase (PARP). And cells transfected with RHCG siRNA exhibited a notable reduction of cleaved Caspase-3 and PARP. Moreover, nucleus nuclear factor-κB (NF-κB) and whole cell xIPA expressions were markedly reduced by over-expressing RHCG. Conversely, suppressing RHCG elevated NF-κB activation and xIPA expression in cervical cancer cells. Notably, we found that TGF-β1 treatment could abolish the effects of RHCG over-expression on the reduction of cell migration and enhancement of apoptosis in cervical cancer cells. Over-expressing RHCG-reduced NF-κB activation and xIPA expression were also abrogated by TGF-β1 pre-treatment. Additionally, enhancing NF-κB activity could restore xIPA expressions and decrease apoptotic response in cervical cancer cells over-expressing RHCG. In vivo, we also found that RHCG over-expression reduced cervical tumor growth through the same signaling pathways as we found in vitro. Therefore, RHCG may be a potential prognostic biomarker and therapeutic target for human cervical cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

l-asparaginase induces intrinsic mitochondrial-mediated apoptosis in human gastric adenocarcinoma cells and impedes tumor progression

Highlights: • We first confirmed that l-asparagine is essential for the growth and proliferation of AGS cells. • We further clarified that l-asparagine deprivation by l-asparaginase promotes anti-proliferation and apoptosis of AGS cells. • We demonstrated that action of l-asparaginase alters mitochondrial membrane permeability and activates intrinsic apoptosis. • We also showed that l-asparaginase impedes tumor progression. l-asparagine essentially regulates growth and proliferation of cancer cells. l-asparaginase is an anti-cancer enzyme that deprives the cancer cells of l-asparagine. The purpose of this study was to explore the mechanism of a novel l-asparaginase from Pseudomonas fluorescens on l-asparagine deprivation mediated anti-proliferation, apoptosis in human gastric adenocarcinoma cells and to evaluate inhibition of angiogenesis. We observed that, the presence of extracellular l-asparagine was essential for the growth of AGS cells. l-asparagine deprivation by l-asparaginase induced metabolic stress, cytotoxicity and apoptosis by G0 phase cell-cycle arrest, modulated the mitochondrial membrane integrity, accelerated caspase-3 activation and instigated DNA damage. The RT-PCR analysis of pro-apoptosis genes: bak1, bax, bbc3, bik, pmaip1, bnip3l, apaf1, casp3, casp7 and casp9 were significantly higher (P xiap, bid, mcl1, and death receptor genes tnf and tradd were significantly down-regulated (P l-asparaginase alters mitochondrial membrane permeability and auxiliary activates intrinsic apoptosis. Therefore, this mechanistic approach might be considered as a targeted enzymotherapy against gastric adenocarcinoma.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

CircRNA circ-BANP-mediated miR-503/LARP1 signaling contributes to lung cancer progression

Recently, circular RNAs (circRNAs) attract much attention due to their potential vital functions in multiple human diseases, including cancer. circ-BANP has been reported to modulate colorectal cancer growth. Nevertheless, the relationship between circ-BANP and lung cancer requires to be investigated. In this study, we found circ-BANP was overexpressed in lung cancer tissues. Higher circ-BANP expression was associated with lower survival rate. Moreover, silencing circ-BANP markedly inhibited proliferation, migration and invasion of lung cancer cells in vitro and impaired tumor propagation in vivo. In mechanism, circ-BANP was identified as the sponge of miR-503 while miR-503 targets LARP1. Circ-BANP-induced inhibition of miR-503 led to increased expression of LARP1 in lung cancer. Finally, rescue assays indicated that LARP1 restoration partially reversed the effects of circ-BANP knockdown in lung cancer. In sum, our study illustrated that circ-BANP-mediated miR-503/LARP1 signaling promoted lung cancer growth, migration and invasion, providing a novel insight on the mechanism underlying lung cancer progression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

DNA copy number gain-mediated lncRNA LINC01061 upregulation predicts poor prognosis and promotes papillary thyroid cancer progression

Several DNA copy number amplifications (CNAs) have been reported in papillary thyroid cancer (PTC). However, the functional role of CNAs in PTC remains very unclear. And whether there is a correlation between long noncoding RNA (lncRNA) and CNA requires to be explored. Here, we identified a novel lncRNA LINC01061. The genomic copy number of LINC01061 is amplified, which leads to its elevated expression level in PTC tissues. Moreover, increased level of LINC01061 was correlated with aggressive clinicopathological characteristics. Functional study indicated that LINC01061 silence significantly inhibited the proliferation, cell-cycle and invasion of PTC cells in vitro and tumor growth in vivo. Mechanistically, we showed that LINC01061 interacted with miR-4316 to promote E2F6 expression. The expression of miR-4316 was downregulated in PTC tissues while that of E2F6 was upregulated. Through rescue assay, we demonstrated that LINC01061 promoted PTC cell proliferation, cell-cycle progression and invasion by regulating miR-4316/E2F6 signaling pathway. In conclusion, our research indicated that LINC01061 might be a target for PTC therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Decreased expression of protein tyrosine kinase 6 contributes to tumor progression and metastasis in laryngeal squamous cell carcinoma

Highlights: • Overexpression of PTK6 significantly decreased cell growth, clonogenicity, invasion and migration capacity in LSCC. • PTK6 suppresses LSCC proliferation mainly by inhibiting c-myc and cyclinD1 expression. • PTK6 promotes cell apoptosis in LSCC. • PTK6 mitigated LSCC invasion and migration through regulating EMT and MMP-9. PTK6 is involved in cell proliferation, invasion and migration. Patients with lower PTK6 expression predicts poor prognosis of LSCC. However, the mechanism of PTK6 in LSCC progression remains unclear. We investigated the role of PTK6 in the pathogenesis of LSCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

miR-181d-5p-FOXP1 feedback loop modulates the progression of osteosarcoma

MicroRNAs (miRNAs) are playing more and more fundamental roles in the progress of human cancers. miR-181d-5p has not been fully elucidated in human cancers. In this study, we aimed to investigate the biological function and mechanism of miR-181d-5p in osteosarcoma (OS). At first, the expression conditions of miR-181d-5p were identified in OS tissues and cell lines. Downregulation of miR-181d-5p was identified to be a significant prognostic factor for patients with OS. Using the bioinformatics analysis, the putative target mRNA (FOXP1) of miR-181d-5p was found out. Similarly, the expression conditions and prognostic value of FOXP1 were identified in OS. To validate the tumor suppressive role of miR-181d-5p in OS, gain or loss of function assays were carried out in OS cell lines. The results indicated the anti-oncogenic function of miR-181d-5p in OS. Subsequently, the oncogenic function of FOXP1 in OS was identified by functional assays. Rescue assays manifested that the oncogenic function of FOXP1 can be partially reversed by miR-181d-5p. Combining with the result of luciferase reporter assay, we confirmed that miR-181d-5p can act as a tumor suppressor in OS via targeting FOXP1. Further mechanism experiments revealed that FOXP1 can suppressed the transcription activity of miR-181d-5p by acting as a transcription inhibitor. In conclusion, our study revealed that miR-181d-5p-FOXP1 feedback loop modulates cell proliferation and metastasis in osteosarcoma.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

CircRNA circHIPK3 serves as a prognostic marker to promote glioma progression by regulating miR-654/IGF2BP3 signaling

Emerging evidences show RNA back-splicing produces a new type of noncoding RNA, namely circular RNA (circRNA). Many reports demonstrate that circRNA circHIPK3 exerts oncogenic or anti-tumor roles in different cancers, such as ovarian cancer, bladder cancer, osteosarcoma, colorectal cancer and liver cancer. However, no study about circHIPK3 function in glioma exists until today. In this study, we showed that circHIPK3 was upregulated in glioma tissues. Elevated level of circHIPK3 was linked to poor prognosis. Functional investigation indicated that circHIPK3 promotes glioma cell proliferation and invasion, and tumor propagation in vivo. Furthermore, miR-654 was identified as a target of circHIPK3 while IGF2BP3 was targeted by miR-654. CircHIPK3 could promote IGF2BP3 expression via interacting with miR-654 in glioma cells. Finally, CCK8 and transwell assays illustrated that IGF2BP3 overexpression could reverse the effects of IGF2BP3 depletion. Altogether, our findings demonstrated that circHIPK3 contributes to glioma progression through targeting miR-654 from IGF2BP3 and implies circHIPK3 might be a potential target for glioma therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

LncRNA LINC00641 predicts prognosis and inhibits bladder cancer progression through miR-197-3p/KLF10/PTEN/PI3K/AKT cascade

As a new group of important effector molecules involved in multiple cancers, long noncoding RNAs (lncRNAs) have attracted much attention recently. Especially, evidences have indicated lncRNAs might be promising biomarkers and targets for cancer therapy. LINC00641 is a novel lncRNA, whose function remains totally unclear. The aim of our study was to determine the functions of LINC00641 in bladder cancer. We found that LINC00641 expression was significantly down-regulated in bladder cancer tissues. Down-regulation of LINC00641 in patients with bladder cancer predicts poor prognosis. Gain-of-function assays indicated that LINC00641 up-regulation markedly inhibited the proliferation, migration and invasion of bladder cancer cells. Xenograft assay also confirmed that LINC00641 overexpression suppressed bladder cancer growth in vivo. Mechanistically, LINC00641 was demonstrated to interact with miR-197-3p, whose target was KLF10. By up-regulating KLF10 level, LINC00641 suppressed the PTEN/PI3K/AKT pathway, leading to prevention of bladder cancer progression. Taken together, our study illustrated a novel signaling cascade of LINC00641/miR-197-3p/KLF10/PTEN/PI3K/AKT pathway regulating bladder cancer development.

60 APPLIED LIFE SCIENCES↗