scholarly journals Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating the microRNA-34a-5p/NOTCH1 signaling pathway

2020 ◽  
Vol 15 (1) ◽  
pp. 284-295
Author(s):  
Yongtian Zhang ◽  
Dandan Zhao ◽  
Shumei Li ◽  
Meng Xiao ◽  
Hongjing Zhou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Signaling Pathway ◽  
Notch Receptor ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Notch1 Signaling ◽  
Non Coding Rna ◽  
Notch1 Signaling Pathway ◽  
Long Non Coding Rna

AbstractMultiple myeloma (MM) is a serious health issue in hematological malignancies. Long non-coding RNA taurine-upregulated gene 1 (TUG1) has been reported to be highly expressed in the plasma of MM patients. However, the functions of TUG1 in MM tumorigenesis along with related molecular basis are still undefined. In this study, increased TUG1 and decreased microRNA-34a-5p (miR-34a-5p) levels in MM tissues and cells were measured by the real-time quantitative polymerase reaction assay. The expression of relative proteins was determined by the Western blot assay. TUG1 knockdown suppressed cell viability, induced cell cycle arrest and cell apoptosis in MM cells, as shown by Cell Counting Kit-8 and flow cytometry assays. Bioinformatics analysis, luciferase reporter assay, and RNA pull-down assay indicated that miR-34a-5p was a target of TUG1 and directly bound to notch receptor 1 (NOTCH1), and TUG1 regulated the NOTCH1 expression by targeting miR-34a-5p. The functions of miR-34a-5p were abrogated by TUG1 upregulation. Moreover, TUG1 loss impeded MM xenograft tumor growth in vivo by upregulating miR-34a-5p and downregulating NOTCH1. Furthermore, TUG1 depletion inhibited the expression of Hes-1, Survivin, and Bcl-2 protein in MM cells and xenograft tumors. TUG1 knockdown inhibited MM tumorigenesis by regulating the miR-34a-5p/NOTCH1 signaling pathway in vitro and in vivo, deepening our understanding of the TUG1 function in MM.

scholarly journals Long Non-Coding RNA MEG3 Functions as a Competing Endogenous RNA to Regulate HOXA11 Expression by Sponging miR-181a in Multiple Myeloma

2018 ◽  
Vol 49 (1) ◽  
pp. 87-100 ◽  
Author(s):  
Xuxing Shen ◽  
Hua Bai ◽  
Huayuan Zhu ◽  
Qing Yan ◽  
Ye Yang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Tumor Formation ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Background/Aims: Long non-coding RNA maternally expressed gene 3 (MEG3) has been reported to play an essential role in cancer progression and metastasis. However, the overall biological role and regulatory mechanism of MEG3 in multiple myeloma (MM) development and progression remains largely ill-defined. Methods: MEG3 and miR-181a expression of MM patients were analyzed by publicly available MM data sets. Cell counting kit-8 and flow cytometry analysis were used to identify the function of MEG3 on MM in vitro. Additionally, we conducted tumor formation experiments in mice models to explain the role of MEG3 on MM in vivo. Then, several mechanism experiments, including dual-luciferase reporter assay and RNA immunoprecipitation were performed to evaluate the emulative relationship between MEG3 and miR-181a. Results: In this research, we found that MEG3 was downregulated in MM patients, which was linked with tumor progression. In addition, we demonstrated that miR-181a was overexpressed in MM patients in consistent with its cancer-promoting function. Importantly, several mechanism experiments revealed that MEG3, acting as an endogenous competitive RNA, could contend with miR-181a to inhibit tumor progression. Furthermore, as the target mRNA of miR-181a, homeobox gene A11(HOXA11) could be positively regulated by MEG3 through sponging miR-181a competitively in vitro. Conclusion: Our present work supplies the first discovery of a MEG3/miR-181a/HOXA11 regulatory network in MM and highlights that MEG3 may serve as a promising target for MM therapy in the future.

scholarly journals Oncogene APOL1 promotes proliferation and inhibits apoptosis via activating NOTCH1 signaling pathway in pancreatic cancer

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Jiewei Lin ◽  
Zhiwei Xu ◽  
Junjie Xie ◽  
Xiaxing Deng ◽  
Lingxi Jiang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Density Lipoprotein ◽  
Human Pancreatic Cancer ◽  
Luciferase Reporter ◽  
Notch1 Signaling ◽  
In Vivo Experiments ◽  
Notch1 Signaling Pathway

AbstractAPOL1 encodes a secreted high-density lipoprotein, which has been considered as an aberrantly expressed gene in multiple cancers. Nevertheless, the role of APOL1 in the regulatory mechanisms of pancreatic cancer remains unknown and should be explored. We identified APOL1 was abnormally elevated in human pancreatic cancer tissues compared with that in adjacent tissues and was associated with poor prognosis. The effects of APOL1 in PC cell proliferation, cell cycle, and apoptosis was verified via functional in vitro and in vivo experiments. The results showed that knockdown of APOL1 significantly inhibited the proliferation and promoted apoptosis of pancreatic cancer. In addition, we identified APOL1 could be a regulator of NOTCH1 signaling pathway using bioinformatics tools, qRT-PCR, dual-luciferase reporter assay, and western blotting. In summary, APOL1 could function as an oncogene to promote proliferation and inhibit apoptosis through activating NOTCH1 signaling pathway expression in pancreatic cancer; therefore, it may act as a novel therapeutic target for pancreatic cancer.

scholarly journals Long non-coding RNA NEAT1/miR-320b/MSI2 axis regulates cisplatin resistance in ovarian cancer

2021 ◽  
Author(s):  
Chunling Zhao ◽  
Pingfen Zi ◽  
Degang Zhou
Keyword(s):  
Ovarian Cancer ◽  
Cell Viability ◽  
Cisplatin Resistance ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Novel Therapy ◽  
Non Coding Rna ◽  
Long Non Coding Rna

IntroductionOvarian cancer (OC) frequently occurs in postmenopausal women and it has higher mortality rate. Accumulating researches proved that long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) involved in the progression of chemoresistance in human OC. Here, the study aimed to investigate the partial molecular mechanism of OC chemoresistance.Material and methodsThe levels of NEAT1 and microRNA-320b (miR-320b) were measured by qRT-PCR. Western blot was carried out to determine the protein levels that used in this research. Cell viability was identified via Cell Counting Kit-8 (CCK-8). Transwell assay was employed to determine migration and invasion. The relationship between miR-320b and NEAT1 or MSI2 was clarified by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and RNA pull down assay. Also, a murine xenograft assay was used to explore the effect of NEAT1 on cisplatin resistance in OC in vivo.ResultsThe level of NEAT1 was significantly increased in cisplatin resistant OC cell lines. Downregulation of NEAT1 enhanced cisplatin sensibility in OVCAR-3/DDP and HEY/DDP cells. Furthermore, miR-320b was a target of NEAT1, and the effects of knockdown of NEAT1 on the cell viability, IC50 of cisplatin, migration and invasion in OVCAR-3/DDP and HEY/DDP were restored by the inhibitor of miR-320. In addition, miR-320b directly targeted MSI2 to regulate cisplatin sensibility in cisplatin resistant OC cells. In addition, downregulation of NEAT1 decreased cisplatin resistance in OC in vivo.ConclusionsNEAT1 regulated cisplatin resistance through NEAT1/miR-320b/MSI2 axis in OC, which might offer a novel therapy target for the chemotherapy of OC.

scholarly journals Transthyretin Upregulates Long Non-Coding RNA MEG3 by Affecting PABPC1 in Diabetic Retinopathy

2019 ◽  
Vol 20 (24) ◽  
pp. 6313 ◽  
Author(s):  
Guangming Fan ◽  
Yu Gu ◽  
Jiaojiao Zhang ◽  
Yu Xin ◽  
Jun Shao ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Retinal Vessel ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Mice Model ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Maternally Expressed Gene 3

The aim of the study was to demonstrate how transthyretin (TTR) could affect long non-coding RNA (lncRNA) of maternally expressed gene 3 (MEG3) and play important roles in diabetic retinopathy (DR). A DR model in C57BL/6 mice was established after intraperitoneal injection of streptozotocin (STZ). After intravitreal injection with TTR pAAV vector, MEG3 short hairpin RNA (shRNA), scrambled shRNA, or MEG3, retinal imaging, retinal trypsin digestion, and fundus vascular permeability tests were performed. Cell counting kit-8 (CCK8), transwell, and Matrigel assays were employed to detect the proliferation and migration of human retinal microvascular endothelial cells (hRECs). The binding between long non-coding RNA of maternally expressed gene 3 (lncRNA-MEG3) and microRNA-223-3p (miR-223-3p) was observed by using luciferase reporter assays, while co-immunoprecipitation (co-IP) was employed to confirm the interaction between TTR and the target. In the DR mice model, retinal vascular leakage and angiogenesis were repressed by overexpressing TTR. In vitro, the added TTR promoted the level of lncRNA-MEG3 by interacting with poly (A) binding protein cytoplasmic 1 (PABPC1), and then repressed proliferation and angiogenesis of hRECs. In vivo, silencing or overexpressing lncRNA-MEG3 significantly affected retinal vascular phenotypes. Additionally, the interaction between lncRNA-MEG3 and miR-223-3p was confirmed, and silencing of miR-223-3p revealed similar effects on hRECs as overexpression of lncRNA-MEG3. In summary, in the DR environment, TTR might affect the lncRNA MEG3/miR-223-3p axis by the direct binding with PABPC1, and finally repress retinal vessel proliferation.

scholarly journals LncRNA PVT1 promotes cervical cancer progression by sponging miR-503 to upregulate ARL2 expression

2021 ◽  
Vol 16 (1) ◽  
pp. 1-13
Author(s):  
Weiwei Liu ◽  
Dongmei Yao ◽  
Bo Huang
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Nude Mouse Model ◽  
Western Blot Assay ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Cervical cancer (CC) is a huge threat to the health of women worldwide. Long non-coding RNA plasmacytoma variant translocation 1 gene (PVT1) was proved to be associated with the development of diverse human cancers, including CC. Nevertheless, the exact mechanism of PVT1 in CC progression remains unclear. Levels of PVT1, microRNA-503 (miR-503), and ADP ribosylation factor-like protein 2 (ARL2) were measured by quantitative reverse transcription-polymerase chain reaction or western blot assay. 3-(4,5)-Dimethylthiazole-2-y1)-2,5-biphenyl tetrazolium bromide (MTT) and flow cytometry were used to examine cell viability and apoptosis, respectively. For migration and invasion detection, transwell assay was performed. The interaction between miR-503 and PVT1 or ARL2 was shown by dual luciferase reporter assay. A nude mouse model was constructed to clarify the role of PVT1 in vivo. PVT1 and ARL2 expressions were increased, whereas miR-503 expression was decreased in CC tissues and cells. PVT1 was a sponge of miR-503, and miR-503 targeted ARL2. PVT1 knockdown suppressed proliferation, migration, and invasion of CC cells, which could be largely reverted by miR-503 inhibitor. In addition, upregulated ARL2 could attenuate si-PVT1-mediated anti-proliferation and anti-metastasis effects on CC cells. Silenced PVT1 also inhibited CC tumor growth in vivo. PVT1 knockdown exerted tumor suppressor role in CC progression via the miR-503/ARL2 axis, at least in part.

Long Non-Coding RNA ARAP1-AS1 Facilitates the Progression of Cervical Cancer by Regulating miR-149-3p and POU2F2

Pathobiology ◽  
2021 ◽  
pp. 1-12
Author(s):  
Ling Zhou ◽  
Xiao-li Xu
Keyword(s):  
Cervical Cancer ◽  
Tumor Model ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Non Coding Rna ◽  
Injection Model ◽  
Rna Immunoprecipitation ◽  
Long Non Coding Rna

<b><i>Background:</i></b> Emerging research has demonstrated that long non-coding RNAs (lncRNAs) attach great importance to the progression of cervical cancer (CC). LncRNA ARAP1-AS1 was involved in the development of several cancers; however, its role in CC is far from being elucidated. <b><i>Methods:</i></b> Real-time PCR (RT-PCR) was employed to detect ARAP1-AS1 and miR-149-3p expression in CC samples. CC cell lines (HeLa and C33A cells) were regarded as the cell models. The biological effect of ARAP1-AS1 on cancer cells was measured using CCK-8 assay, colony formation assay, flow cytometry, Transwell assay and wound healing assay in vitro, and subcutaneous xenotransplanted tumor model and tail vein injection model in vivo. Furthermore, interactions between ARAP1-AS1 and miR-149-3p, miR-149-3p and POU class 2 homeobox 2 (POU2F2) were determined by bioinformatics analysis, qRT-PCR, Western blot, luciferase reporter and RNA immunoprecipitation assay, respectively. <b><i>Results:</i></b> The expression of ARAP1-AS1 was enhanced in CC samples, while miR-149-3p was markedly suppressed. Additionally, ARAP1-AS1 overexpression enhanced the viability, migration, and invasion of CC cells. ARAP1-AS1 downregulated miR-149-3p via sponging it. ARAP1-AS1 and miR-149-3p exhibited a negative correlation in CC samples. On the other hand, ARAP1-AS1 enhanced the expression of POU2F2, which was validated as a target gene of miR-149-3p. <b><i>Conclusion:</i></b> ARAP1-AS1 was abnormally upregulated in CC tissues and indirectly modulated the POU2F2 expression via reducing miR-149-3p expression. Our study identified a novel axis, ARAP1-AS1/miR-149-3p/POU2F2, in CC tumorigenesis.

scholarly journals Long non-coding RNA PTPRG-AS1 promotes cell tumorigenicity in epithelial ovarian cancer by decoying microRNA-545-3p and consequently enhancing HDAC4 expression

2020 ◽  
Author(s):  
Juanjuan Shi ◽  
Xijian Xu ◽  
Dan Zhang ◽  
Jiuyan Zhang ◽  
Hui Yang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Epithelial Ovarian Cancer ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Background: Long non-coding RNA PTPRG antisense RNA 1 (PTPRG-AS1) deregulation has been reported in various human malignancies and identified as an important modulator of cancer development. Few reports have focused on the detailed role of PTPRG-AS1 in epithelial ovarian cancer (EOC) and its underlying mechanism. This study aimed to determine the physiological function of PTPRG-AS1 in EOC. A series of experiments were also performed to identify the mechanisms through which PTPRG-AS1 exerts its function in EOC.Methods: Reverse transcription-quantitative polymerase chain reaction was used to determine PTPRG-AS1 expression in EOC tissues and cell lines. PTPRG-AS1 was silenced in EOC cells and studied with respect to cell proliferation, apoptosis, migration, and invasion in vitro and tumor growth in vivo. The putative miRNAs that target PTPRG-AS1 were predicted using bioinformatics analysis and further confirmed in luciferase reporter and RNA immunoprecipitation assays.Results: Our data verified the upregulation of PTPRG-AS1 in EOC tissues and cell lines. High PTPRG-AS1 expression was associated with shorter overall survival in patients with EOC. Functionally, EOC cell proliferation, migration, invasion in vitro, and tumor growth in vivo were suppressed by PTPRG-AS1 silencing. In contrast, cell apoptosis was promoted by loss of PTPRG-AS1. Regarding the mechanism, PTPRG-AS1 could serve as a competing endogenous RNA in EOC cells by decoying microRNA-545-3p (miR-545-3p), thereby elevating histone deacetylase 4 (HDAC4) expression. Furthermore, rescue experiments revealed that PTPRG-AS1 knockdown-mediated effects on EOC cells were, in part, counteracted by the inhibition of miR-545-3p or restoration of HDAC4.Conclusions: PTPRG-AS1 functioned as an oncogenic lncRNA that aggravated the malignancy of EOC through the miR-545-3p/HDAC4 ceRNA network. Thus, targeting the PTPRG-AS1/miR-545-3p/HDAC4 pathway may be a novel strategy for EOC anticancer therapy.

scholarly journals Long non-coding RNA LINC00641 promotes the growth and invasiveness of hepatocellular carcinoma by antagonizing miR-501-3p

2021 ◽  
Author(s):  
Haitao Xie ◽  
Hui Zhou ◽  
Yan Jiang ◽  
Wenqian Xu ◽  
Leping Zeng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Normal Liver ◽  
In Vivo Studies ◽  
Luciferase Reporter ◽  
Normal Tissues ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Proliferation And Invasion ◽  
Hcc Cells

IntroductionLong non-coding RNA LINC00641 has been reported to regulate tumor progression in several cancers. However, the expression and function of LINC00641 in hepatocellular carcinoma (HCC) is still unclear.Material and methodsIn this study, we measured the expression of LINC00641 in 79 pairs of HCC and adjacent normal liver tissues. The clinical significance of LINC00641 in HCC was explored. We also investigated the function of LINC00641 in HCC proliferation and invasion.ResultsWe observed that LINC00641 expression was significantly increased in HCC relative to normal tissues (P < 0.0001). High expression of LINC00641 was significantly associated with vascular invasion, advanced TNM stage, and reduced overall survival in HCC patients. Knockdown of LINC00641 inhibited the proliferation, colony formation, and invasion of HCC cells. In contrast, overexpression of LINC00641 promoted HCC cell growth and invasiveness. In vivo studies confirmed that knockdown of LINC00641 restrained tumorigenesis of HCC cells. Mechanistic studies revealed that LINC00641 inhibited the expression of miR-501-3p, which has been previously reported to act as a tumor suppressor in HCC. Furthermore, luciferase reporter assays validated that LINC00641 harbored a target site for miR-501-3p. Rescue experiments demonstrated that LINC00641-induced proliferation and invasion of HCC cells was reversed by co-expression of miR-501-3p.ConclusionsTaken together, LINC00641 contributes to aggressive phenotype of HCC cells by sponging miR-501-3p and represents a promising therapeutic target for this disease.

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