scholarly journals circSMARCA5 Promoted Osteosarcoma Cell Proliferation, Adhesion, Migration, and Invasion through a Competing Endogenous RNA Network

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Hepeng Zhang ◽  
Fanyu Meng ◽  
Shuaicheng Dong

Osteosarcoma (OS) is a widely common sort among bone cancer in children, and its overall survival ratio is low. The hidden mechanism of tumor genesis, progression, and metastasis regarding osteosarcoma needed to be further investigated. Emerging studies concentrated on exploring the functional roles of circular RNAs (circRNAs) in human cancers. The present study conducted a loss-of-function experiments to explore the circSMARCA5-induced influence on OS proliferation, cell cycle, and metastasis. Moreover, our manuscript unearthed the potential mechanisms of circSMARCA5 in regulating OS progression by in silico analysis. Our findings would provide new evidence to support that circSMARCA5 could be indicated as a biomarker for OS.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Luyao Wu ◽  
Yu Ding ◽  
Houchao Tong ◽  
Xi Zhuang ◽  
Jingsheng Cai ◽  
...  

Abstract Background Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in various cancers. However, the functional roles of most lncRNA in papillary thyroid cancer (PTC) are not detailly understood. This study aims to investigate the biological function and molecular mechanism of lncRNA Fer-1 like family member 4 (FER1L4) in PTC. Methods The expression of FER1L4 in PTC was determined via operating quantitative real-time PCR assays. Meanwhile, the clinical significance of FER1L4 in patients with PTC was described. The biological functions of FER1L4 on PTC cells were evaluated by gain and loss of function experiments. Moreover, animal experiments were performed to reveal the effect on tumor growth. Subcellular distribution of FER1L4 was determined by fluorescence in situ hybridization and subcellular localization assays. Luciferase reporter assay and RNA immunoprecipitation assay were applied to define the relationship between FER1L4, miR-612, and Cadherin 4 (CDH4). Results Upregulated expression of FER1L4 in PTC tissues was positively correlated with lymph node metastasis (P = 0.020), extrathyroidal extension (P = 0.013) and advanced TNM stages (P = 0.013). In addition, knockdown of FER1L4 suppressed PTC cell proliferation, migration, and invasion, whereas ectopic expression of FER1L4 inversely promoted these processes. Mechanistically, FER1L4 could competitively bind with miR-612 to prevent the degradation of its target gene CDH4. This condition was further confirmed in the rescue assays. Conclusions This study first demonstrates FER1L4 plays an oncogenic role in PTC via a FER1L4-miR-612-CDH4 axis and may provide new therapeutic and diagnostic targets for PTC.


2021 ◽  
Vol 11 (8) ◽  
pp. 1466-1476
Author(s):  
Xuli Wang ◽  
Aiping Wang

Circular RNAs (circRNAs) have been reported to participate in the molecular mechanism of human cancers. This study investigates the role of circRNA hsa_circ_0000515 in gastric cancer (GC) cells and the underlying mechanism associated with microRNA-615-5p (miR-615-5p). qRT-PCR analysis showed the upregulation of hsa_circ_0000515 and downregulation of miR-615-5p in GC cell lines. Loss-of-function experiments indicated that suppression of hsa_circ_0000515 inhibited cell proliferation, migration, and invasion. Dual-luciferase reporter assay highlighted that hsa_circ_0000515 was able to act as a ceRNA of miR-615-5p. Furthermore, hsa_circ_0000515 could interact with splicing factors and bind miR-615-5p to regulate progression of GC cells. Deficiency of miR-615-5p reverses the inhibitory roles of si-hsa_circ_0000515 on the proliferation, migration, and invasion of GC cells. The findings highlighted the promising uses of hsa_circ_0000515 as a likely novel target for gastric cancer treatment.


2020 ◽  
Vol 19 ◽  
pp. 153303382094321
Author(s):  
Rui Gu ◽  
Xiaodong Li ◽  
Xiaowei Yan ◽  
Zhen Feng ◽  
Aixin Hu

Circular RNAs are a recently discovered subclass of endogenous noncoding RNAs that have been confirmed to play an important role in various pathophysiological processes. However, the underlying function of circular RNAs in osteosarcoma still remains unclear. We aimed to comprehend the function of circ_0032462 in osteosarcoma, as it has been predicted to be highly expressed in osteosarcoma cells. Using real-time polymerase chain reaction, we verified the elevated expression of circ_0032462 in osteosarcoma cells than normal cells. Functional validation experiments revealed that circ_0032462 overexpression promoted proliferation, migration, and invasion in osteosarcoma cells, whereas circ_0032462 silencing was observed to inhibit cancer cell progression (proliferation, migration, and invasion). Furthermore, we found that circ_0032462 upregulated the messenger RNA and protein expression level of kinesin family member 3B. In addition, kinesin family member 3B inhibition was found to inhibit circ_0032462-induced enhanced osteosarcoma cell progression. circ_0032462 overexpression was observed to reverse circ_0032462 silencing-induced inhibitory effect on osteosarcoma cell progression. Overall, our research revealed the function of circ_0032462 in osteosarcoma progression, which might serve as a novel chemotherapeutic target for osteosarcoma.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Juan Cai ◽  
Zhiqiang Chen ◽  
Xueliang Zuo

Background. Circular RNAs have been implicated in various malignancies and can function as potential biomarkers for cancers. Reportedly, circSMARCA5 was downregulated in hepatocellular carcinoma and glioblastoma multiforme, but upregulated in prostate cancer. The functional roles and clinical significance of circSMARCA5 still remain unknown in the context of gastric cancer (GC). Methods. Expression levels of circSMARCA5 were detected by qRT-PCR. Clinical data including patient basic information, clinicopathological features, and survival data were obtained. The Kaplan-Meier methods, multivariate Cox regression models, and the receiver operating characteristic curve were used to assess the clinical significance of circSMARCA5 in GC. Cell proliferation assays and transwell assays were performed to elucidate the functional roles of circSMARCA5 in GC. Results. The circSMARCA5 level was decreased in GC tissues and cell lines. The low expression level of circSMARCA5 was correlated to poorer overall survival and disease-free survival. Low circSMARCA5 expression was revealed as an independent unfavorable predictive factor for GC. The results indicated that circSMARCA5 had a moderate ability for discrimination between GC patients and controls with an area under the curve of 0.806. Upregulation of circSMARCA5 dampened the proliferation, migration, and invasion of GC cells, whereas circSMARCA5 knockdown promoted GC progression. Discussion. Our results demonstrated that circSMARCA5 was decreased and exerted tumor-suppressive effects in GC. circSMARCA5 can function as a potential biomarker for GC prognosis and diagnosis.


2021 ◽  
Author(s):  
Weiqian Chen ◽  
Liyun Zheng ◽  
Songquan Wu ◽  
Chenying Lu ◽  
Bufu Tang ◽  
...  

Abstract Background: Cholangiocarcinoma (CCA) is an aggressive malignancy with a poor prognosis, with no effective therapy other than surgical resection. Circular RNAs (circRNAs) serve as a brand-new class of transcription products among abundant cancer processes. Nevertheless, the mechanisms account for their modification in CCA remain unknown. Methods: First, microarray sequencing was applied to detect the difference of circRNAs expression between CCA and corresponding non-tumor tissues. We utilized qRT-PCR to measure circ-0006302 levels in CCA cells and specimens. Gain/loss of-function assays and animal model of CCA were performed for the purpose of revealing the functions of circ-0006302 on the invasion, migration, and proliferation of CCA. We performed dual luciferase reporter, RNA-FISH and rescue assays for clarifying the mechanism behind. Results: In CCA tissues and cell lines circ-0006302 was highly expressed relatively. In vitro, overexpression of circ-0006302 intensifies the epithelial-to-mesenchymal transition (EMT) and the invasion, migration, and growth of CCA cells; and intensifies the growth as well as metastasis of tumors in a CCA mouse model. Furthermore, it was elucidated that circ-0006302 sponged miR-1299 to upregulate PD‐L1 expression. Through the process above, circ-0006302 binds to miR-1299 and emancipates PD-L1, facilitating the invasion, migration, and proliferation in CCA cells. Momentously, the results obtained revealed that circ-0006302 silencing elevated the expression of interferon (IFN)‐γ, and interleukin (IL)‐4 but diminished the IL-10 expression, while these effects could be reversed by miR-1299 inhibitor.Conclusion: circ-0006302 silence blocked the CCA progression via intensifying miR‐1299‐targeted downregulation of PD‐L1. Our conclusion provides novel therapeutic tactics for treating this fatal disease.


Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 25 ◽  
Author(s):  
Ebrahim Mahmoudi ◽  
Dylan Kiltschewskij ◽  
Chantel Fitzsimmons ◽  
Murray J. Cairns

Circular RNAs (circRNAs) are a relatively new class of RNA transcript with high abundance in the mammalian brain. Here, we show that circRNAs expression in differentiated neuroblastoma cells were significantly altered after depolarization with 107 upregulated and 47 downregulated circRNAs. This coincided with a global alteration in the expression of microRNA (miRNA) (n = 269) and mRNA (n = 1511) in depolarized cells, suggesting a regulatory axis of circRNA–miRNA–mRNA is involved in the cellular response to neural activity. In support of this, our in silico analysis revealed that the circular transcripts had the capacity to influence mRNA expression through interaction with common miRNAs. Loss-of-function of a highly expressed circRNA, circ-EXOC6B, resulted in altered expression of numerous mRNAs enriched in processes related to the EXOC6B function, suggesting that circRNAs may specifically regulate the genes acting in relation to their host genes. We also found that a subset of circRNAs, particularly in depolarized cells, were associated with ribosomes, suggesting they may be translated into protein. Overall, these data support a role for circRNAs in the modification of gene regulation associated with neuronal activity.


2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Si Chen ◽  
Weiguo Li ◽  
Ai Guo

Abstract lncRNA LOXL1 antisense RNA 1 (lncRNA LOXL1-AS1) was recently found to function as oncogenic lncRNA in glioblastoma, prostate cancer, and medulloblastoma. The role of LOXL1-AS1 in osteosarcoma was still unknown. In our study, we found LOXL1-AS1 expression levels were higher in osteosarcoma tissues and cell lines than normal bone tissues and normal osteoblast cell line, respectively. Moreover, high-expression of LOXL1-AS1 was correlated with Enneking stage, tumor size, distant metastasis, histological grade, and overall survival time in osteosarcoma patients. Furthermore, LOXL1-AS1 overexpression acted as an independent poor predictor for overall survival in osteosarcoma patients. The loss-of-function studies showed knockdown of LOXL1-AS1 dramatically inhibited osteosarcoma cell proliferation, migration, and invasion through suppressing PI3K-AKT pathway. In conclusion, LOXL1-AS1 predicts clinical progression and poor prognosis in osteosarcoma patients and functions as oncogenic lncRNA to regulate cell proliferation, cell cycle, migration, and invasion.


2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Bao-Long Pan ◽  
Ling Wu ◽  
Li Pan ◽  
Yu-Xi Yang ◽  
Hu-Huan Li ◽  
...  

Osteosarcoma (OS) is the most common histological form of primary bone cancer. It is most prevalent in teenagers and young adults. The present study aims at exploring the regulatory effect of microRNA-340 (miR-340) on OS cell proliferation, invasion, migration, and apoptosis via regulating the Notch signaling pathway by targeting β-catenin (cadherin-associated protein) 1 (CTNNB1). OS tissues belonging to 45 patients and normal femoral head tissues of 45 amputees were selected. Cells were allocated to different groups. In situ hybridization was performed to determine the positive rate of miR-340 expression while immunohistochemistry was used to determine that of CTNNB1 and B-cell lymphoma 2 (Bcl-2). We used a series of experiments to measure the expressions of related factors and assess rates of cell proliferation, migration, invasion, cycle, and apoptosis respectively. Our results show that miR-340 was expressed a higher level in normal tissue than OS tissue. Expression of Notch, CTNNB1, hairy and enhancer of split 1 (Hes1), Bcl-2, Runt-related transcription factor 2 (Runx2), and osteocalcin increased and that of miR-340, Bcl-2 interacting mediator of cell death (BIM), and Bcl-2 associated protein X (Bax) decreased in OS tissues. U-2OS cell line had the highest miR-340 expression. We also found that the up-regulation of miR-340 had increased expression of miR-340, BIM, and Bax but decreased expression of Notch, CTNNB1, Hes1, Bcl-2, Runx2, and osteocalcin. Up-regulation of miR-340p lead to increased cell apoptosis, suppressed cell proliferation, migration, and invasion. Our study demonstrates that overexpression of miR-340 could suppress OS cell proliferation, migration, and invasion as well as promoting OS cell apoptosis by inactivating the Notch signaling pathway via down-regulating CTNNB1. Functional miR-340 overexpression might be a future therapeutic strategy for OS.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Erhu Lin ◽  
Shuai Liu ◽  
Wei Xiang ◽  
Hongbo Zhang ◽  
Chaofan Xie

Circular RNAs (circRNAs) play a key role in regulating the tumorigenesis and development of human cancers, including osteosarcoma (OS). Of note, the molecular mechanism underlying the progression of OS has remained largely unclear. The present study identified that a novel circRNA circEIF4G2 was upregulated in OS tissues and cells. Moreover, we constructed a circEIF4G2-mediated ceRNA network and revealed that circEIF4G2 was involved in regulating multiple cancer pathways, such as the EGFR signaling pathway, the PI3K-Akt signaling pathway, and the ErbB signaling pathway. Loss-of-function assays showed that circEIF4G2 knockdown significantly suppressed OS cell proliferation, migration, and invasion. Mechanically, we found that circEIF4G2 could directly bind to miR-218, and miR-218 mediated the effect of circEIF4G2 knockdown on OS progression. In conclusion, the present study showed that circEIF4G2 could be a potential biomarker for OS.


2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Shian Liao ◽  
Sijia Zhou ◽  
Chao Wang

Gastric adenocarcinoma predictive long intergenic non-coding (GAPLINC) is a novel long non-coding RNA (lncRNA) and has been found to function as an oncogenic lncRNA in gastric cancer, colorectal cancer, and bladder cancer. The expression status and biological function of GAPLINC in osteosarcoma are still unknown. Thus, we analyzed the association between GAPLINC expression and clinicopathological characteristics in osteosarcoma clinical samples, and conducted loss-of-function study in osteosarcoma cell lines. In our results, GAPLINC expression is elevated in osteosarcoma tissues and cell lines, and correlated with advanced Enneking stage, present distant metastasis, and poor histological grade. Survival analyses indicated that GAPLINC expression was negatively associated with overall survival, and GAPLINC high-expression was an independent risk factor in osteosarcoma patients. The in vitro studies showed knockdown of GAPLINC depressed osteosarcoma cell migration and invasion via inhibiting CD44 expression, but no effect on cell proliferation. In conclusion, GAPLINC may serve as a potential biomarker for predicting prognosis and developing therapy for osteosarcoma.


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