scholarly journals circITGA7 Functions as an Oncogene by Sponging miR-198 and Upregulating FGFR1 Expression in Thyroid Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Siqi Li ◽  
Junmei Yang ◽  
Xiaoting Liu ◽  
Rui Guo ◽  
Ruidong Zhang
Keyword(s):  
Thyroid Cancer ◽  
Cell Lines ◽  
Circular Rna ◽  
Clinical Findings ◽  
Circular Rnas ◽  
Potential Marker ◽  
And Function ◽  
Functional Analyses ◽  
Fgfr1 Expression

Background. Emerging evidence has indicated that circular RNAs (circRNAs), recognized as functional noncoding transcripts in eukaryotic cells, may be involved in regulating many physiological or pathological processes. However, the regulation and function of circular RNA circITGA7 in thyroid cancer (TC) remains unknown. Methods. In this study, we found that circITGA7 is upregulated in TC cell lines. We then performed functional analyses in the cell lines to support clinical findings. Mechanistically, we demonstrated that circITGA7 can directly bind to miR-198 and reduce the inhibition effect of miR-198 on target FGFR1 expression. Results. We reported an upregulation of circITGA7 in patients with TC. Silencing of circITGA7 inhibits metastasis and proliferation of TC cell lines in vitro. In addition, in the TC cell lines, the knockdown of circITGA7 or overexpression of miR-198 significantly suppressed FGFR1 levels. Mechanistically, we found that circITGA7 acts as miR-198 competitive endogenous RNA (ceRNA) to regulate FGFR1 expression. Conclusions. In summary, circRNA circITGA7 may play a regulatory role in TC and may be a potential marker for TC diagnosis or progression.

scholarly journals Circular RNA circRUNX1 promotes papillary thyroid cancer progression and metastasis by sponging MiR-296-3p and regulating DDHD2 expression

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Junjie Chu ◽  
Li Tao ◽  
Teng Yao ◽  
Zizheng Chen ◽  
Xiaoxiao Lu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Cancer Progression ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Papillary Thyroid ◽  
Promoting Effect

AbstractPapillary thyroid cancer (PTC) has a continuously increasing incidence and imposes a heavy medical burden to individuals and society due to its high proportion of lymph node metastasis and recurrence in recent years. Circular RNAs, a class of noncoding RNAs, participate in the progression of many cancers, but the role of circRNAs in PTC is still rarely reported. In this study, circRNA deep sequencing was performed to identify differentially expressed circRNAs in PTC. CircRUNX1 was selected for its high expression in PTC, and circRUNX1 silencing was directly associated with the week potential for migration, invasion and proliferation of PTC in vivo and in vitro. Fluorescence in situ hybridization (FISH) was further used to confirm the cytoplasmic localization of circRUNX1, indicating the possible function of circRUNX1 as a ceRNAs in PTC progression through miRNA binding. MiR-296-3p was then confirmed to be regulated by circRUNX1 and to target DDHD domain containing 2 (DDHD2) by luciferase reporter assays. The strong antitumor effect of miR-296-3p and the tumor-promoting effect of DDHD2 were further investigated in PTC, indicating that circRUNX1 modulates PTC progression through the miR-296-3p/DDHD2 pathway. Overall, circRUNX1 plays an oncogenic role in PTC and provides a potentially effective therapeutic strategy for PTC progression.

scholarly journals Circular RNA circ_001422 promotes the progression and metastasis of osteosarcoma via the miR-195-5p/FGF2/PI3K/Akt axis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Bingsheng Yang ◽  
Lutao Li ◽  
Ge Tong ◽  
Zhirui Zeng ◽  
Jianye Tan ◽  
...  
Keyword(s):  
Cell Lines ◽  
Clinical Stage ◽  
Distant Metastases ◽  
Bioinformatic Analysis ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Advanced Clinical Stage

Abstract Background Circular RNAs (circRNAs) are involved in diverse processes that drive cancer development. However, the expression landscape and mechanistic function of circRNAs in osteosarcoma (OS) remain to be studied. Methods Bioinformatic analysis and high-throughput RNA sequencing tools were employed to identify differentially expressed circRNAs between OS and adjacent noncancerous tissues. The expression level of circ_001422 in clinical specimens and cell lines was measured using qRT-PCR. The association of circ_001422 expression with the clinicopathologic features of 55 recruited patients with OS was analyzed. Loss- and gain-of-function experiments were conducted to explore the role of circ_001422 in OS cells. RNA immunoprecipitation, fluorescence in situ hybridization, bioinformatics database analysis, RNA pulldown assays, dual-luciferase reporter assays, mRNA sequencing, and rescue experiments were conducted to decipher the competitive endogenous RNA regulatory network controlled by circ_001422. Results We characterized a novel and abundant circRNA, circ_001422, that promoted OS progression. Circ_001422 expression was dramatically increased in OS cell lines and tissues compared with noncancerous samples. Higher circ_001422 expression correlated with more advanced clinical stage, larger tumor size, higher incidence of distant metastases and poorer overall survival in OS patients. Circ_001422 knockdown markedly repressed the proliferation and metastasis and promoted the apoptosis of OS cells in vivo and in vitro, whereas circ_001422 overexpression exerted the opposite effects. Mechanistically, competitive interactions between circ_001422 and miR-195-5p elevated FGF2 expression while also initiating PI3K/Akt signaling. These events enhanced the malignant characteristics of OS cells. Conclusions Circ_001422 accelerates OS tumorigenesis and metastasis by modulating the miR-195-5p/FGF2/PI3K/Akt axis, implying that circ_001422 can be therapeutically targeted to treat OS.

scholarly journals Circular RNA circSIPA1L1 Contributes to Osteosarcoma Progression via the miR-411-5p/RAB9A Axis

2020 ◽  
Author(s):  
Yining Xu ◽  
Teng Yao ◽  
Haonan Ni ◽  
Rujie Zheng ◽  
Kangmao Huang ◽  
...  
Keyword(s):  
Real Time ◽  
Cell Lines ◽  
Mrna Level ◽  
Circular Rna ◽  
Tumor Promoter ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Driver Gene

Abstract BackgroundRecently, various studies have identified circular RNAs (circRNAs) to play a significant role in tumorigenesis, thereby showing potential as novel tumor biomarkers. circSIPA1L1 is a new-found circular RNA formed by back-splicing of SIPA1L1 and is found increased in osteosarcoma (OS). Nevertheless, the specific functions of circSIPA1L1 in OS remain unknown. MethodsIn the present study, circSIPA1L1 was obtained from a previously reported circRNA microarray (GSE96964) in the GEO database. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess the mRNA level of circSIPA1L1 in OS cell lines and tissue samples. Bioinformatics analysis, luciferase reporter assays, real-time PCR, RNA pull-down assays and RNA immunoprecipitation (RIP) were employed to verify the binding of circSIPA1L1 with miR-411-5p. Xenograft tumor models were established to identify the role of circSIPA1L1 in vivo. A series of in-vitro experiments, such as western blotting , colony formation, transwell assays and anoikis assay were employed to confirm the relationship across circSIPA1L1, miR-411-5p, and RAB9A. ResultsOur study confirmed circSIPA1L1 to be upregulated in both human OS samples and OS cell lines. Mechanistically, circSIPA1L1 could serve as a miR-411-5p molecular sponge to increase RAB9A expression, which was confirmed to be a tumor promoter mediating carcinogenesis. Silencing of circSIPA1L1 attenuated the vitality, invasion, migration and proliferation of OS cell lines both in vivo and in vitro. miR-411-5p inhibition or RAB9A overexpression reversed the anti-tumor effects caused by circSIPA1L1 knockdown. ConclusionBriefly, circSIPA1L1 acts as a driver gene in OS and could initiate OS tumorigenesis via the miR-411-5p/RAB9A axis, which might become a potential therapeutic biomarker for OS treatment.

scholarly journals Hsa_circ_0005273 facilitates breast cancer tumorigenesis by regulating YAP1-hippo signaling pathway

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Xuehui Wang ◽  
Changle Ji ◽  
Jiashu Hu ◽  
Xiaochong Deng ◽  
Wenfang Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Potential Biomarker

Abstract Background Circular RNAs (circRNAs), a novel class of endogenous RNAs, have shown to participate in the development of breast cancer (BC). Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functional role of hsa_circ_0005273 in BC remains largely unknown. Here we aim to evaluate the role of hsa_circ_0005273 in BC. Methods The expression level of hsa_circ_0005273 and miR-200a-3p were examined by RT-qPCR in BC tissues and cell lines. The effect of knocking down hsa_circ_0005273 in BC cell lines were evaluated by examinations of cell proliferation, migration and cell cycle. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. RNA immunoprecipitation assay, RNA probe pull-down assay, luciferase reporter assay and fluorescence in situ hybridization were conducted to confirm the relationship between hsa_circ_0005273, miR-200a-3p and YAP1. Results Hsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of hsa_circ_0005273 inhibited the progression of BC cells in vitro and in vivo, while overexpression of hsa_circ_0005273 exhibited the opposite effect. Importantly, hsa_circ_0005273 upregulated YAP1 expression and inactivated Hippo pathway via sponging miR-200a-3p to promote BC progression. Conclusions Hsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and inactivates Hippo signaling pathway to promote BC progression, which may become a potential biomarker and therapeutic target.

scholarly journals Grafts Derived from an α-Synuclein Triplication Patient Mediate Functional Recovery but Develop Disease-Associated Pathology in the 6-OHDA Model of Parkinson’s Disease

2020 ◽  
pp. 1-14
Author(s):  
Shelby Shrigley ◽  
Fredrik Nilsson ◽  
Bengt Mattsson ◽  
Alessandro Fiorenzano ◽  
Janitha Mudannayake ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Lines ◽  
Functional Recovery ◽  
Embryonic Stem ◽  
Hesc Line ◽  
Alternative Source ◽  
And Function

Background: Human induced pluripotent stem cells (hiPSCs) have been proposed as an alternative source for cell replacement therapy for Parkinson’s disease (PD) and they provide the option of using the patient’s own cells. A few studies have investigated transplantation of patient-derived dopaminergic (DA) neurons in preclinical models; however, little is known about the long-term integrity and function of grafts derived from patients with PD. Objective: To assess the viability and function of DA neuron grafts derived from a patient hiPSC line with an α-synuclein gene triplication (AST18), using a clinical grade human embryonic stem cell (hESC) line (RC17) as a reference control. Methods: Cells were differentiated into ventral mesencephalic (VM)-patterned DA progenitors using an established GMP protocol. The progenitors were then either terminally differentiated to mature DA neurons in vitro or transplanted into 6-hydroxydopamine (6-OHDA) lesioned rats and their survival, maturation, function, and propensity to develop α-synuclein related pathology, were assessed in vivo. Results: Both cell lines generated functional neurons with DA properties in vitro. AST18-derived VM progenitor cells survived transplantation and matured into neuron-rich grafts similar to the RC17 cells. After 24 weeks, both cell lines produced DA-rich grafts that mediated full functional recovery; however, pathological changes were only observed in grafts derived from the α-synuclein triplication patient line. Conclusion: This data shows proof-of-principle for survival and functional recovery with familial PD patient-derived cells in the 6-OHDA model of PD. However, signs of slowly developing pathology warrants further investigation before use of autologous grafts in patients.

Survival and Function of Fibroblasts Stored as Stock Cultures at a Non-freezing Temperature

1993 ◽  
Vol 21 (2) ◽  
pp. 206-209
Author(s):  
Anders H. G. Andrén ◽  
Anders P. Wieslander
Keyword(s):  
Cell Growth ◽  
Cell Line ◽  
Cell Lines ◽  
Fibroblast Cell ◽  
Freezing Temperature ◽  
Mouse Fibroblast ◽  
Toxic Response ◽  
Normal Manner ◽  
And Function

Cytotoxicity, measured as inhibition of cell growth of cultured cell lines, is a widely used method for testing the safety of biomaterials and chemicals. One major technical disadvantage with this method is the continuous routine maintenance of the cell lines. We decided to investigate the possibility of storing stock cultures of fibroblasts (L-929) in an ordinary refrigerator as a means of reducing the routine workload. Stock cultures of the mouse fibroblast cell line L-929 were prepared in plastic vials with Eagle's minimum essential medium. The vials were stored in a refrigerator at 4–10°C for periods of 7–31 days. The condition of the cells after storage was determined as cell viability, cell growth and the toxic response to acrylamide, measured as cell growth inhibition. We found that the L-929 cell line can be stored for 2–3, weeks with a viabilty > 90% and a cell growth of about 95%, compared to L-929 cells grown and subcultured in the normal manner. The results also show that the toxic response to acrylamide, using refrigerator stored L-929 cells, corresponds to that of control L-929 cells. We concluded that it is possible to store L-929 cells in a refrigerator for periods of up to 3 weeks and still use the cells for in vitro cytotoxic assays.

scholarly journals Efficacy and Biomarker Analysis of Adavosertib in Differentiated Thyroid Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3487
Author(s):  
Yu-Ling Lu ◽  
Ming-Hsien Wu ◽  
Yi-Yin Lee ◽  
Ting-Chao Chou ◽  
Richard J. Wong ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Lines ◽  
Differentiated Thyroid Cancer ◽  
Xenograft Model ◽  
In Vivo Studies ◽  
Follicular Thyroid Cancer ◽  
Biomarker Analysis ◽  
Cancer Tumor

Differentiated thyroid cancer (DTC) patients are usually known for their excellent prognoses. However, some patients with DTC develop refractory disease and require novel therapies with different therapeutic mechanisms. Targeting Wee1 with adavosertib has emerged as a novel strategy for cancer therapy. We determined the effects of adavosertib in four DTC cell lines. Adavosertib induces cell growth inhibition in a dose-dependent fashion. Cell cycle analyses revealed that cells were accumulated in the G2/M phase and apoptosis was induced by adavosertib in the four DTC tumor cell lines. The sensitivity of adavosertib correlated with baseline Wee1 expression. In vivo studies showed that adavosertib significantly inhibited the xenograft growth of papillary and follicular thyroid cancer tumor models. Adavosertib therapy, combined with dabrafenib and trametinib, had strong synergism in vitro, and revealed robust tumor growth suppression in vivo in a xenograft model of papillary thyroid cancer harboring mutant BRAFV600E, without appreciable toxicity. Furthermore, combination of adavosertib with lenvatinib was more effective than either agent alone in a xenograft model of follicular thyroid cancer. These results show that adavosertib has the potential in treating DTC.

scholarly journals Expression and function of the novel proto-oncogene PBF in thyroid cancer: a new target for augmenting radioiodine uptake

2011 ◽  
Vol 210 (2) ◽  
pp. 157-163 ◽  
Author(s):  
Vicki E Smith ◽  
Jayne A Franklyn ◽  
Christopher J McCabe
Keyword(s):  
Thyroid Cancer ◽  
Current Data ◽  
Subcellular Localisation ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Radioiodine Uptake ◽  
Novel Target ◽  
And Function

Pituitary tumor-transforming gene (PTTG)-binding factor (PBF; PTTG1IP) was initially identified through its interaction with the human securin, PTTG. Like PTTG, PBF is upregulated in multiple endocrine tumours including thyroid cancer. PBF is believed to induce the translocation of PTTG into the cell nucleus where it can drive tumourigenesis via a number of different mechanisms. However, an independent transforming ability has been demonstrated both in vitro and in vivo, suggesting that PBF is itself a proto-oncogene. Studied in only a limited number of publications to date, PBF is emerging as a protein with a growing repertoire of roles. Recent data suggest that PBF possesses a complex multifunctionality in an increasing number of tumour settings. For example, PBF is upregulated by oestrogen and mediates oestrogen-stimulated cell invasion in breast cancer cells. In addition to a possible role in the induction of thyroid tumourigenesis, PBF overexpression in thyroid cancers inhibits iodide uptake. PBF has been shown to repress sodium iodide symporter (NIS) activity by transcriptional regulation of NIS expression through the human NIS upstream enhancer and further inhibits iodide uptake via a post-translational mechanism of NIS governing subcellular localisation. This review discusses the current data describing PBF expression and function in thyroid cancer and highlights PBF as a novel target for improving radioiodine uptake and thus prognosis in thyroid cancer.

scholarly journals Thymosin-β4 Mediates Hepatic Stellate Cell Activation by Interfering with CircRNA-0067835/miR-155/FoxO3 Signaling Pathway

2018 ◽  
Vol 51 (3) ◽  
pp. 1389-1398 ◽  
Author(s):  
Lili Zhu ◽  
Tingting Ren ◽  
Zixin Zhu ◽  
Mingliang  Cheng ◽  
Qiuju Mou ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Cell Activation ◽  
Stellate Cell ◽  
Circular Rna ◽  
Fine Tuning ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
G1 Arrest

Background/Aims: Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrosis. Our study proved that thymosin beta 4 (Tβ4) has anti-fibrogenic effects in HSCs through PI3K/AKT pathway. However, the underlying mechanisms are not fully elucidated. Circular RNAs (circRNAs) play important roles in fine-tuning gene expression and are often deregulated in cancers. However, the expression profile and clinical significance of in liver fibrosis is still unknown. Therefore, we hypothesize that Tβ4 influences circRNAs in liver fibrosis. Methods: Circular RNA microarray was conducted to identify Tβ4-related circRNAs. Pathway analysis and miRNA response elements analysis was conducted to predict the potential roles of differentially expressed circRNAs in liver fibrosis. CCK8 assays and flow cytometric assays were conducted to clarify the role of circRNA in liver fibrosis. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in liver fibrosis. Results: A total of 644 differentially expressed circRNAs were identified between the Tβ4-depleted LX-2 cells and the control LX2 cells. The expression of circRNA-0067835 was significantly increased in the Tβ4-depleted LX-2 cells compared with control. Knockdown of circRNA-0067835 observably decreased LX-2 cell proliferation by causing G1 arrest and promoting apoptosis. Bioinformatics online programs predicted that circRNA-0067835 acted as miR-155 sponge to regulate FOXO3a expression, which was validated using luciferase reporter assay. Conclusion: Our experiments showed that circRNA-0067835 regulated liver fibrosis progression by acting as a sponge of miR-155 to promote FOXO3a expression, indicating that circRNA-0067835 may serve as a potential therapeutic target for patients with liver fibrosis.

scholarly journals Circular RNA circFAT1(e2) Promotes Colorectal Cancer Tumorigenesis via the miR-30e-5p/ITGA6 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Fei Pan ◽  
Dongqing Zhang ◽  
Na Li ◽  
Mei Liu
Keyword(s):  
Colorectal Cancer ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Small Interfering Rnas ◽  
Regulatory Relationship ◽  
Downstream Target ◽  
Normal Tissues

circRNAs (circular RNAs) are a family of noncoding RNAs and have diverse physiological and pathological functions. However, the functions and mechanisms of circRNAs in the development and progression of colorectal cancer (CRC) remain largely unknown. Here, we aimed to explore the functions and roles of circFAT1(e2) in CRC. qRT-PCR revealed that circFAT1(e2) in CRC tumor tissues was upregulated compared with that in adjacent normal tissues and was also upregulated in CRC cell lines. Small interfering RNAs (siRNAs) against circFAT1(e2) were used to decrease the expression of circFAT1(e2) in HCT116 and RKO cells in vitro. The roles of circFAT1(e2) in CRC cell metastasis and proliferation were then determined by transwell and CCK-8 assays. The results showed that circFAT1(e2) silencing markedly suppressed CRC growth. Moreover, we identified circFAT1(e2) as a promoter of CRC metastasis. Knockdown of circFAT1(e2) evidently reduced HCT116 and RKO cell migration and invasion. Furthermore, the regulatory relationship between circFAT1(e2) and its target miRNAs was verified by a luciferase reporter assay. We demonstrated that circFAT1(e2) could sponge miR-30e-5p, which regulated the expression level of integrin α6 (ITGA6), the downstream target gene of miR-30e-5p. Rescue assays demonstrated that knockdown of miR-30e-5p enhanced CRC proliferation and migration via ITGA6. Taken together, our results reveal the novel oncogenic roles of circFAT1(e2) in CRC through the miR-30e-5p/ITGA6 axis.

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