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At least 811 records · Page 45
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

The up-regulation of long non-coding RNA CCAT2 indicates a poor prognosis for prostate cancer and promotes metastasis by affecting epithelial-mesenchymal transition

Recently, long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in human cancer biology. LncRNA CCAT2 is a novel identified lncRNA that was previously reported to be up-regulated in different cancers, however, its role in prostate cancer remains unclear. The aim of this study was to investigate the expression and role of lncRNA CCAT2 in prostate cancer. The expression levels of lncRNA CCAT2 in PCa tissues and cell lines (DU145 and 22RV1) were evaluated by quantitative real-time PCR (qRT-PCR), and its association with prognosis of patients was analyzed by statistical analysis. Furthermore, the effect of CCAT2 on proliferation, migration, and invasion was studied in PCa cells. We found that the expression level of CCAT2 was higher in PCa tissues and cells compared to adjacent non-tumor tissues and normal prostate stromal immortalized cells WPMY-1. Kaplan-Meier survival analysis revealed that patients with high CCAT2 expression level had poorer overall survival and progression-free survival than those with low CCAT2 expression. Furthermore, multivariate analysis showed that the status of CCAT2 expression was an independent prognostic indicator for this disease. We also found that knockdown of CCAT2 could inhibit cell growth, migration, and invasion in vitro. In addition, knockdown of CCAT2 stimulated epithelial-mesenchymal transition (EMT) through abrogating N-cadherin, vimentin expression and intensifing the expression levels of E-cadherin. In conclusion, our data suggested that lncRNA CCAT2 was a novel molecule involved in PCa progression, which provided a potential prognostic biomarker and therapeutic target for new therapies in patients with prostate cancer. - Highlights: • LncRNA CCAT2 is identified with overexpression in prostate cancer tissues and cell lines. • High expression of lncRNA CCAT2 can be an independent prognostic factor for overall survival and progression-free survival. • Knockdown of lncRNA CCAT2 can inhibit cell growth, migration, and invasion in vitro study. • Knockdown of lncRNA CCAT2 stimulates metastasis of prostate cancer cell through regulating EMT-associated gene expression including N-cadherin, Vimentin and E-cadherin.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Long non-coding RNA linc-cdh4-2 inhibits the migration and invasion of HCC cells by targeting R-cadherin pathway

Long non-coding RNAs (LncRNAs) have played very important roles in the malignancy behaviors of hepatocellular carcinoma (HCC). Linc-cdh4-2 (TCONS-00027978) is a novel LncRNA that has been identified in HCC tissues from our previous study. Overexpression of linc-cdh4-2 in HCC cell lines (SK-Hep-1 and Huh7) significantly decreases the migration and invasion abilities of these cells, while knockdown the expression of linc-cdh4-2 significantly increases the migration and invasion abilities. Interestingly, neither the over expression nor the knock down of linc-cdh4-2 could affect the viability and proliferation of HCC cells. Mechanistically, the linc-cdh4-2 could up-regulate the protein level of R-cadherin through direct binding that might improve the protein stability. Over expression of linc-cdh4-2 could significantly increase the protein levels of R-cadherin and decrease the protein levels of small GTPase RAC1, and vice-versa. Further knockdown R-cadherin in linc-cdh4-2 stably overexpressed cells, could significantly upregulate the protein levels of RAC1 and improve the cell migration and invasion abilities. Taken together, the novel linc-cdh4-2 may negatively regulate the motility of the HCC cells through targeting R-cadherin-RAC1 signaling pathway. - Highlights: • Linc-cdh4-2 negatively related with the invasion and metastasis ability of HCC cells. • Linc-cdh4-2 could up-regulate the protein level of R-cadherin through direct binding. • Knockdown of R-cadherin increases the migration and invasion abilities of HCC cell. • Knockdown of R-cadherin could significantly upregulate the protein levels of RAC1.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Long non-coding RNA ENST00462717 suppresses the proliferation, survival, and migration by inhibiting MDM2/MAPK pathway in glioma

Gliomas are the most common and aggressive primary malignant tumor in the central nervous system, and requires new biomarkers and therapeutic methods. Long noncoding RNAs (lncRNAs) are important factors in numerous human diseases, including cancer. But studies on lncRNAs and gliomas are limited. In this study, we investigated the expression patterns of lncRNAs in 3 pairs of glioma samples and adjacent non-tumor tissues via microarray and selected the most down-regulated lnc00462717 to further verify its roles in glioma. We observed that decreased lnc00462717 expression was associated with the malignant status in glioma. In vitro experiment demonstrated that lnc00462717 overexpression suppressed glioma cell proliferation, survival and migration while knockdown of lnc00462717 had an opposite result. Moreover, we identified MDM2 as a direct target of lnc00462717 and lnc00462717 played a role by partially regulating the MDM2/MAPK pathway. In conclusion, lnc00462717 may function in suppressing glioma cell proliferation, survival, migration and may potentially serve as a novel biomarker and therapeutic target for glioma. - Highlights: • Using microarray to investigate the expression patterns of lncRNAs in glioma. • Selecting the most down-regulated lnc00462717 via microarray to verify its roles. • Identifying MDM2 as a direct target of lnc00462717. • The mechanism of lnc00462717 regulating the MDM2/MAPK pathway. • lnc00462717 serve as a novel biomarker and therapeutic target for treating glioma.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

PART-1 functions as a competitive endogenous RNA for promoting tumor progression by sponging miR-143 in colorectal cancer

LncRNAs were altered in several cancers and played a crucial role in various biological activities and progressions of different diseases, including proliferation, chemical resistance, and metastasis. In the present study, we revealed that prostrate androgen-regulated transcript-1 (PART-1) was highly expressed in colorectal cancer cells and tissues, and knockdown of PART-1 suppressed cell proliferation and metastasis, both in vitro and in vivo. In addition, PART-1 functioned as a ceRNA of DNMT3A, by sponging miR-143. Finally,PART-1 induced tumor progression by regulating DNMT3A. - Highlights: • Prostrate androgen-regulated transcript-1 (PART-1) was highly expressed in colorectal cancer cells and tissues. • Knockdown of PART-1 suppressed cell proliferation and metastasis, both in vitro and in vivo. • PART-1 functioned as a ceRNA of DNMT3A, by sponging miR-143. • PART-1 induced tumor progression by regulating DNMT3A.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Upregulated long non-coding RNA LOC90784 promotes cell proliferation and invasion and is associated with poor clinical features in HCC

A growing amount of literature has indicated that long non-coding RNAs (lncRNAs) are important factors in hepatocellular carcinoma (HCC) progression. However, the significance of lncRNAs in the progression and prognosis of liver cancer is largely unknown. In the present study, upregulated lncRNA LOC90784 was identified through integrative analysis of (GSE58043) and (GSE55191). Furthermore, associations between LOC90784 expression and the clinicopathological characteristics of patients were analyzed with a validated cohort 1 and the Cancer Genome Atlas (TCGA) cohort 2. We investigated the mechanisms by which this highly expressed lncRNA promotes HCC proliferation, invasion and migration via qRT-PCR, fluorescence in situ hybridization (FISH) staining, siRNA transfection, cell proliferation assays, Transwell and colony formation assays, flow cytometry analysis and Western blot. The results showed that LOC90784 expression levels were significantly higher in HCC cell lines and tissues and mainly localized in the cytoplasm. Knockdown of lncRNA LOC90784 expression inhibited proliferation and induced apoptosis and cell cycle arrest by promoting Bax and repressing CDK4 and Cyclin D1 protein expression; it also inhibited invasion and migration by repressing MMP2 and MMP9 expression in HCC cells. LOC90784 overexpression was associated with poor clinical features in the two cohorts and poor overall survival rates in HCC patients with clear resection margins (R0) in cohort 2. These results indicated that LOC90784 upregulation may be a critical oncogene and potential new biomarker in HCC. - Highlights: • LncRNA LOC90784 was overexpressed in HCC tissues and cell lines. • Highly expressed lncRNA LOC90784 was associated with poor clinical features in HCC. • Knockdown of lncRNA LOC90784 expression inhibited proliferation and induced apoptosis and cell cycle arrest. • Knockdown of lncRNA LOC90784 expression inhibited invasion and migration.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Long noncoding RNA linc00346 promotes the malignant phenotypes of bladder cancer

Background: More and more reports have demonstrated that long noncoding RNAs (lncRNAs) play an important role in the development of a variety of carcinomas, including bladder cancer. However, only a small fraction of them have been characterized. Linc00346 have been found to be upregulated in bladder cancer tissues compared to normal tissues in a microarray-based lncRNA profiling study. In this study, we would like to explore the expression pattern and functional role of linc00346 in bladder cancer. Methods: We determined the expression of linc00346 in a cohort of bladder cancer tissues with matched normal tissues as well as human bladder cancer cell lines. We investigated the biological function of linc00346 with CCK-8 assay, colony formation assay, flow cytometry analysis, transwell assay and tumor xenografts mice model. Results: We found that linc00346 was upregulated in bladder cancer tissues compared to normal tissues. Knockdown of linc00346 inhibited bladder cancer cell proliferation and migration, induced cell cycle arrest and cell apoptosis. Conclusion: Our study demonstrates that linc00346 could be a potential oncogene and a therapeutic target in bladder cancer. - Highlights: • linc00346 was upregulated in bladder cancer tissues compared to normal tissues. • linc00346 promoted bladder cancer cell proliferation and migration. • Knockdown of linc00346 induced cell cycle arrest and cell apoptosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Long non-coding RNA PCAT7 regulates ELF2 signaling through inhibition of miR-134-5p in nasopharyngeal carcinoma

While some long noncoding RNAs (lncRNAs) might promote nasopharyngeal carcinoma (NPC) initiation and progression, the involved molecular mechanisms remain largely unclear. Here, we discovered the novel LncRNA, prostate cancer associated transcript 7 (PCAT7), which was overexpressed and associated with worse prognosis in NPC. Decreased PCAT7 expression was found to significantly suppress tumor cell proliferation in vitro, and inhibited tumor growth and reduced the expression of proliferation antigen Ki-67 in vivo. Rescue assay was performed to further confirm that PCAT7 contributed to the progression of NPC through regulating miR-134-5p/ELF2 signal pathway. These results indicated that PCAT7 might contribute to the tumor progression in NPC by functioning as a ceRNA to sponge miR-134-5p. - Highlights: • PCAT7 is up-regulated in human primary NPC tissues. • Expression of ELF2 is up-regulated in primary human NPC and negatively expressed related to miR-134-5p. • MiR-134-5p inhibits the tumorigenic potential of NPC cells by down-regulating oncogenic ELF2 gene. • PCAT7's oncogenic functions are partially through reverse regulation of miRNA-134-5p, and then activation of ELF2.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Long non-coding RNA-422 acts as a tumor suppressor in colorectal cancer

Highlights: • LncRNA-422 in CRC tissues was significantly lower than that in adjacent tissues. • The expression of lncRNA-422 was correlated with TNM stage of CRC. • LncRNA-422 inhibits the proliferation, migration and invasion of CRC cells. • LncRNA-422 acts as a tumor suppressor by PI3K/AKT/mTOR pathway in CRC. Colorectal cancer (CRC) is one of the most frequent cancer in numerous of countries worldwidely. The initiation and progression of CRC is an extremely complex process, and have been suggested a correlation with Long non-coding RNAs (lncRNAs). Our results showed that lncRNA-422(ENST00000415820) significantly downregulated in the tissues and serum of CRC patients, and is closely associated with the poor prognosis. Then gain or loss of lncRNA-422 models in SW480 and SW620cells were established. The results showed that lncRNA-422 overexpression inhibited cell proliferation, migration, and invasion. Knockdown of lncRNA-422 promoted tumorigensis. Western blot and qRT-PCR were performed to examine the activity of the PI3K/AKT/mTOR pathway in CRC cells after alternation of lncRNA-422. Results showed that lncRNA-422 acts as a tumor suppressor by PI3K/AKT/mTOR pathway in CRC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

C/EBPβ contributes to transcriptional activation of long non-coding RNA NEAT1 during APL cell differentiation

Emerging evidences have shown that long non-coding RNAs (lncRNAs) play critical roles in cancer development and cancer therapy. LncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) is indispensable during acute promyelocytic leukemia (APL) cell differentiation induced by all-trans retinoic acid (ATRA). However, the precise mechanism of NEAT1 upregulation has not been fully understood. In this study, we performed chromatin immunoprecipitation and luciferase reporter assays to demonstrate that C/EBP family transcription factor C/EBPβ bind to and transactivate the promoter of lncRNA NEAT1 through the C/EBPβ binding sites both around −54 bp and −1453 bp upstream of the transcription start site. Moreover, the expression of C/EBPβ was increased after ATRA treatment, and the binding of C/EBPβ in the NEAT1 promoter was also dramatically increased. Finally, knockdown of C/EBPβ significantly reduced the ATRA-induced upregulation of NEAT1. In conclusion, C/EBPβ directly activates the expression of NEAT1 through binding to the promoter of NEAT1. Knockdown of C/EBPβ impairs ATRA-induced transcriptional activation of NEAT1. Our data indicate that C/EBPβ contributes to ATRA-induced activation of NEAT1 during APL cell differentiation. Our results enrich our knowledge on the regulation of lncRNAs and the regulatory role of C/EBPβ in APL cell differentiation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Long non-coding RNA LUCAT1 modulates methotrexate resistance in osteosarcoma via miR-200c/ABCB1 axis

Highlights: • LncRNA LUCAT1 and ABCB1 protein are both up-regulated in osteosarcoma methotrexate-resistant cells. • LncRNA LUCAT1 knockdown suppress the expression levels drug resistance related genes, proliferation, invasion and tumor growth of osteosarcoma cells in vitro and vivo. • Bioinformatics predictive tools and luciferase assay reveal the LUCAT1/miR-200c/ABCB1 pathway. • Rescue experiments confirm the combined role of LUCAT1, miR-200c and ABCB1 on osteosarcoma methotrexate resistance. Long non-coding RNAs (lncRNAs) have been verified to participate in the tumorigenesis of multiple cancers. Nevertheless, the deepgoing role molecular mechanisms of lncRNAs on osteosarcoma chemoresistance remain unclear. In present study, we investigate the function of lncRNA LUCAT1 on osteosarcoma methotrexate (MTX) resistant phenotype and discover the potential regulatory mechanism. Results showed that LUCAT1 was up-regulated in MTX-resistant cells (MG63/MTX, HOS/MTX) compared to that in parental cells. LncRNA LUCAT1 and ABCB1 protein expression levels were both up-regulated when induced by different concentration of methotrexate. In vitro and vivo, LUCAT1 knockdown decreased the expression levels drug resistance related genes (MDR1, MRP5, LRP1), proliferation, invasion and tumor growth of osteosarcoma cells. Bioinformatics tools and luciferase assay reveled that miR-200c both targeted the 3′-UTR of LUCAT1 and ABCB1 mRNA, suggesting the modulation of LUCAT1 on ABCB1 through sponging miR-200c. Rescue experiments confirmed the combined role of LUCAT1, miR-200c and ABCB1 on osteosarcoma proliferation, invasion and methotrexate resistance. Overall, results indicate the vital role of LUCAT1 in the methotrexate resistance regulation through miR-200c/ABCB1 pathway, providing a novel insight and treatment strategy for osteosarcoma drug resistance.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Circular RNA expression profiles in placental villi from women with gestational diabetes mellitus

Highlights: • More than 40,000 circRNAs are sequenced in the placental villi. • The expression profile of circRNAs in GDM is different from that in controls. • The potential effects of many differential circRNAs are involve in the development of GDM. • Some differential circRNAs have binding sites of GDM-related miRNAs. Circular RNAs (circRNAs) have recently been shown to exert their effects on multiple pathological processes by acting as microRNA (miRNA) sponges. However, the roles of circRNAs in gestational diabetes mellitus (GDM) are largely unknown. This study aimed to identify the circRNAs involved in GDM and predict their potential biological functions. We first performed next-generation sequencing (NGS) to generate unbiased placental villi circRNA expression profiles of GDM and normal controls. In total, 48,270 circRNAs from the placental villi of the two groups were sequenced. Of these, 227 circRNAs were significantly up-regulated and 255 circRNAs were significantly down-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses demonstrated that glycometabolism and lipometabolism processes, which are important in GDM development, were significantly enriched. Further analysis showed that most of the circRNAs harbored miRNA binding sites, and some were associated with GDM. These results showed that circRNAs are aberrantly expressed in the placental villi of GDM patients and play potential roles in the development of GDM.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Circular RNA circMAN2B2 facilitates lung cancer cell proliferation and invasion via miR-1275/FOXK1 axis

Highlights: • CircMAN2B2 knockdown suppresses lung cancer cell proliferation and invasion. • CircMAN2B2 sponges and represses miR-1275 expression in lung cancer. • miR-1275 exerts its role by regulation of FOXK1 expression in lung cancer. • CircMAN2B2 promotes lung cancer cell proliferation an invasion via circMAN2B2/miR-1275/FOXK1 signaling. Lung cancer remains a leading cause of cancer-related deaths worldwide. In the past years, increasing reports indicate that circular RNAs (circRNAs) exert a great important role in human cancers, including lung cancer. However, the knowledge about circRNA in lung cancer remains very little so far. In the present study, we screened out a highly expressed novel circRNA named circMAN2B2 in lung cancer tissues. We investigated the function of circMAN2B2 and found that circMAN2B2 knockdown significantly inhibited cell proliferation and invasion in both H1299 and A549 lung cancer cells. Mechanistically, we found that circMAN2B2 could sponge miR-1275 to inhibit its level. Through a series of functional experiments, we dissected the role of miR-1275 in lung cancer and proved the anti-tumor role of miR-1275. Furthermore, we found that miR-1275 exerted its role in lung cancer by regulating FOXK1 expression. In addition, we demonstrated that restoration of FOXK1 could rescue circMAN2B2 knockdown-induced repression of cell proliferation and invasion. Taken together, our study demonstrated that circMAN2B2 acts as an oncogenic role in lung cancer through promoting FOXK1 expression by sponging miR-1275.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Long noncoding RNA lncARSR promotes hepatic lipogenesis via Akt/SREBP-1c pathway and contributes to the pathogenesis of nonalcoholic steatohepatitis

Highlights: • The expression of lncARSR increased in NAFLD patients and mouse model. • lncARSR modulated hepatic lipid accumulation in vivo and in vitro. • SREBP-1c mediated the effect of lncARSR on lipognesis in NASH. • lncARSR regulated SREBP-1c via PI3K/Akt pathway. Non-alcoholic fatty liver disease and steatohepatitis (NAFLD and NASH) account for the majority of liver disease in industrialized countries. However, the pathogenesis still unclear. Long non-coding RNAs (lncRNAs) has been reported to be involved in various pathophysiological processes. Here, we reported a novel role of lncARSR in hepatic lipogenesis in NAFLD. The expression of lncARSR was induced both in NAFLD patients and mouse model, as well as in hepatocytes treated with fatty acid. Moreover, overexpression of lncARSR enhanced while knockdown of lncARSR ameliorated hepatic lipid accumulation in vivo and in vitro. Furthermore, the expression of genes related to fatty acid synthesis and oxidation increased with lncARSR overexpression in vivo. Mechanistically, we identified that lncARSR regulated hepatic lipogenesis via upregulating SREBP-1c, the key regulatory molecule involved in lipogenesis. Knockdown of SREBP-1c by shRNA blocked the effect of lncARSR on lipogenesis. Furthermore, we demonstrated that lncARSR regulated SREBP-1c expression by PI3K/Akt pathway. In conclusion, our data indicated that lncARSR potentially contributes to the hepatic steatosis in NAFLD, which may be a new therapeutic target against NAFLD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Identification of aberrant circular RNA expression and its potential clinical value in primary great saphenous vein varicosities

Highlights: • This study identified 232 significantly aberrant circRNAs in primary great saphenous vein varicosities (PGSVVs). • A circRNA-miRNA-gene co-expression network was created. • Hsa{sub c}irc{sub 0}006427, hsa{sub c}irc{sub 0}089810 and hsa{sub c}irc{sub 0}005267 might be potential biological markers for PGSVVs. This study aimed to identify aberrant circRNA expression in primary great saphenous vein varicosities (PGSVVs) and investigate its potential clinical significance. High-throughput sequencing was applied to analyze the differential expression of circRNAs in three paired vein samples of PGSVVs and a control group. Computational bioinformatics analyses, including gene ontology (GO) analysis and encyclopedia of genes and genomes (KEGG) pathway analysis, were performed to further enrich microRNA data. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to verify the selected aberrant circRNAs in all vein samples, and a receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic and potential clinical significance. A total of 232 circRNAs were significantly aberrantly expressed in PGSVVs, including 105 and 127 upregulated and downregulated circRNAs, respectively. The predicted top 10 downstream miRNAs of the significantly altered circRNAs are hsa-miR-103a-2-5p, hsa-miR-141-5p, hsa-miR-3692-5p, hsa-miR-4659a-3p, hsa-miR-4659b-3p, hsa-miR-4691-5p, hsa-miR-4778-3p, hsa-miR-6738-3p, hsa-miR-6792-3p and hsa-miR-6873-3p. GO analysis revealed that the most enriched and meaningful biological process, cellular component, and molecular function terms were related to the regulation of catabolic processes, the cytoplasm and ATP binding, respectively. The most enriched and meaningful pathways revealed by KEGG pathway analysis were related to “axon guidance” “vitamin digestion and absorption” and “NF-Kappa B signaling pathway”. Hsa{sub c}irc{sub 0}006427 (P = 0.007), hsa{sub c}irc{sub 0}089810 (P = 0.044) and hsa{sub c}irc{sub 0}005267 (P = 0.049) were significantly downregulated in the PGSVV group relative to their expression levels in the control group, and the area under the ROC curve was 0.9091, 0.8025 and 0.8148, respectively. This study demonstrated that circRNAs were differentially expressed in PGSVVs, and highlights the crucial roles of circRNAs in the pathogenesis of PGSVVs and indicates that hsa{sub c}irc{sub 0}006427, hsa{sub c}irc{sub 0}089810 and hsa{sub c}irc{sub 0}005267 might be potential diagnostic and clinical biological markers.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Long noncoding RNA LNC473 inhibits the ubiquitination of survivin via association with USP9X and enhances cell proliferation and invasion in hepatocellular carcinoma cells

Highlights: • LNC473 was overexpressed in HCC tissues and correlated with tumor size, BCLC stage, vascular invasion and poor prognosis. • LNC473 enhanced HCC cell proliferation and invasion and induced epithelial–mesenchymal transition (EMT) process. • LNC473 associated with oncoprotein survivin and regulates its stability. • LNC473 recruited USP9X to inhibit survivin ubiquitination and then increase its expression. Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Recent studies reported that lncRNA LINC00473 (LNC473) was involved in cancer progression. However, the clinical significance and functional role of LNC473 in HCC progression is still unknown. In the present study, we found that the LNC473 expression was markedly elevated in HCC tissues and correlated with bigger tumor size, higher BCLC stage, vascular invasion and poor prognosis. Gain- and loss-of-function assay showed that LNC473 enhanced HCC cell proliferation and invasion and induced epithelial–mesenchymal transition (EMT) process. Mechanistically, LNC473 associated with oncoprotein survivin and regulates its stability. Moreover, LNC473 could recruit deubiquitinase USP9X to inhibit the ubiquitination level of survivin and then increase survivin expression. Therefore, our results suggest that LNC473 exerts its functions as an oncogene in HCC progression and may be a therapeutic target for HCC treatment.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Circular RNA circC3P1 suppresses hepatocellular carcinoma growth and metastasis through miR-4641/PCK1 pathway

Highlights: • CircC3P1 was downregulated in HCC tissues. • CircC3P1 overexpression suppressed HCC growth and migration in vitro and in vivo. • CircC3P1 promoted PCK1 expression by sponging miR-4641 in HCC. • CircC3P1 regulated HCC cell proliferation, migration and invasion via modulating PCK1 expression. In the recent years, increasing evidences identify circular RNAs (circRNAs) as a class of important regulators in various human cancers. Nevertheless, the functions and mechanisms of most circRNAs in cancer cells remain largely unknown. In this study, we found out a significantly downregulated circRNA circC3P1 in hepatocellular carcinoma (HCC) tissues compared to adjacent normal tissues. And our results indicated that circC3P1 expression level was negatively correlated with TNM stage, tumor size and vascular invasion in HCC. Moreover, we found that circC3P1 overexpression dramatically inhibited the proliferation, migration and invasion of HCC cells in vitro and in vivo. In terms of mechanism, we found that circC3P1 could promote PCK1 expression through sponging miR-4641 in HCC cells. We showed that miR-4641 expression was negatively correlated with that of either circC3P1 or PCK1 in HCC tissues. Finally, by functional experiments, we demonstrated that knockdown of PCK1 significantly attenuated the effects of circC3P1 overexpression on HCC cell proliferation, migration and invasion. In summary, our findings illustrated that circC3P1 acts as a tumor suppressor via enhancing PCK1 expression by sponging miR-4641 in HCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Circular RNA hsa{sub c}irc{sub 0}000673 promotes hepatocellular carcinoma malignance by decreasing miR-767-3p targeting SET

Highlights: • Hsa{sub c}irc{sub 0}000673 was highly expressed in HCC tissues. • Hsa{sub c}irc{sub 0}000673 knockdown suppressed HCC cell proliferation and invasion. • Hsa{sub c}irc{sub 0}000673 promoted HCC proliferation and invasion by sponging miR-767-3p. • Hsa{sub c}irc{sub 0}000673 facilitated HCC cell proliferation and invasion via regulating miR-767-3p/SET pathway. The importance of circular RNAs (circRNAs) in human cancers has gradually been acknowledged. In hepatocellular carcinoma (HCC), several circRNAs have been reported to regulate tumor growth and metastasis. However, the role of hsa{sub c}irc{sub 0}000673 in HCC remains largely unknown. In this study, we found that hsa{sub c}irc{sub 0}000673 was significantly upregulated in HCC tissues compared to adjacent non-tumor tissues. Moreover, we found that hsa{sub c}irc{sub 0}000673 knockdown markedly inhibited the proliferation and invasion of HCC cells in vitro. Besides, hsa{sub c}irc{sub 0}000673 silence led to delayed tumor growth in vivo. In terms of mechanism, we showed that hsa{sub c}irc{sub 0}000673 directly associated with miR-767-3p in HCC cells. Via inhibiting miR-767-3p, hsa{sub c}irc{sub 0}000673 promoted HCC cell proliferation and invasion. Furthermore, we demonstrated that SET was a downstream effector of hsa{sub c}irc{sub 0}000673/miR-767-3p signaling. We showed that miR-767-3p could significantly promote SET expression by sponging miR-767-3p in HCC cells. Finally, rescue assays indicated that SET expression was essential for the effects of hsa{sub c}irc{sub 0}000673/miR-767-3p signaling on HCC cell proliferation and invasion. Taken together, our findings demonstrated that hsa{sub c}irc{sub 0}000673 promoted HCC malignant behaviors via regulating miR-767-3p/SET pathway.

60 APPLIED LIFE SCIENCES↗