scholarly journals Long non-coding RNA LINC00346 contributes to cisplatin resistance in nasopharyngeal carcinoma by repressing miR-342-5p

Open Biology ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 190286 ◽  
Author(s):  
Zheqing Cui ◽  
Tian Pu ◽  
Yujie Zhang ◽  
Jia Wang ◽  
Yulin Zhao
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cisplatin Resistance ◽  
Chemotherapy Resistance ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Over Expression ◽  
Non Coding Rna ◽  
Rna Immunoprecipitation ◽  
Cisplatin Sensitivity ◽  
Long Non Coding Rna

Cisplatin has been used as the first-line chemotherapy to treat advanced nasopharyngeal carcinoma (NPC), while acquired cisplatin resistance resulting from epigenetic regulation is not well understood. The relative expression of LINC00346 was detected in healthy persons, cisplatin-sensitive (CS) patients and cisplatin-resistant (CR) patients. The regulatory effect of LINC00346 on the proliferation was detected by cell-counting kit-8. Apoptosis was assayed by histone/DNA ELISA and Caspase-3 activity. Clonal formation and cisplatin resistance were also deciphered. Luciferase reporter and RNA immunoprecipitation assay were adopted to study the interaction between LINC00346 and miR-342-5p. LINC00346 was highly expressed in NPC patients, especially in CR patients, which was associated with cisplatin resistance and poor prognosis. Inhibition of LINC00346 expression promoted cisplatin sensitivity of NPC cells, while LINC00346 over-expression promoted cisplatin resistance of NPC cells. miR-342-5p expression was negatively correlated with cisplatin resistance, and microRNA-342-5p siRNAs treatment could rescue the cisplatin resistance diminished by LINC00346 inhibition. It was further found that miR-342-5p was negatively regulated by LINC00346. In conclusion, LINC00346 regulates the cisplatin resistance of NPC cells by inhibiting miR-342-5p, which could provide a potential target for chemotherapy resistance.

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 MiR-34c Downregulation Leads to SOX4 Overexpression and Cisplatin Resistance in Nasopharyngeal Carcinoma

2020 ◽  
Author(s):  
Pierre-Antoine Bissey ◽  
Mona Teng ◽  
Jacqueline H Law ◽  
Wei Shi ◽  
Jeff P Bruce ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epithelial To Mesenchymal Transition ◽  
Cisplatin Resistance ◽  
Chemotherapy Resistance ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
Over Expression ◽  
Tgfβ Receptor ◽  
Cisplatin Sensitivity

Abstract Background : A major cause of disease-related death in nasopharyngeal carcinoma (NPC) is the development of distant metastasis (DM) despite combination chemoradiotherapy treatment. We previously identified and validated a four microRNA (miRNA) signature that is prognostic for DM. In this study, characterization of a key component of this signature, miR-34c, revealed its role in chemotherapy resistance. Methods: 246 NPC patient biopsy samples were subject to comprehensive miRNA profiling and immunohistochemistry (IHC). Two human normal nasopharyngeal cell lines (immortalized; NP69 and NP460), as well as the NPC cell line C666-1, were used to generate pre-miR-34c (gain-of-function) and anti-miR-34c (loss-of-function) cells. Signaling pathways were assessed using quantitative real-time PCR (qRT-PCR) and Western blot. Cell viability was measured using the ATPlite assay. Results: MiR-34c was downregulated in NPC patient samples, and confirmed in vitro to directly target SOX4, a master regulator of epithelial-to-mesenchymal transition (EMT). MiR-34c downregulation triggered EMT-representative changes in NP69 and NP460 whereby Snail, ZEB1, CDH2, and SOX2 were upregulated, while Claudin-1 and CDH1 were downregulated. Phenotypically, inhibition of miR-34c led to cisplatin resistance, whereas miR-34c over-expression sensitized NPC cells to cisplatin. TGFβ1 decreased miR-34c and increased SOX4 expression in vitro . The TGFβ receptor 1 inhibitor SB431542 reduced SOX4 expression and increased cisplatin sensitivity. Finally, IHC revealed that lower SOX4 expression was associated with improved overall survival in chemotherapy-treated NPC patients. Conclusion: miR-34c downregulation correlates with higher incidence of DM. Repression of miR-34c was shown to increase SOX4 expression, which leads to cisplatin resistance, while TGFβ1 was found to repress miR-34c expression. Taken together, our study demonstrates that inhibition of the TGFβ1 pathway could be a strategy to restore cisplatin sensitivity in NPC.

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 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 Downregulation of long non-coding RNA ZXF1 restricts cell survival by targeting miR-634-GRB2 in lung adenocarcinoma

2020 ◽  
Author(s):  
Xubin Ren ◽  
Nie Xu ◽  
Yunting Zhang ◽  
Tao Wang
Keyword(s):  
Lung Adenocarcinoma ◽  
Luciferase Reporter ◽  
Normal Tissues ◽  
Non Coding Rna ◽  
Enhanced Expression ◽  
Rna Immunoprecipitation ◽  
Underlying Mechanisms ◽  
First Time ◽  
Long Non Coding Rna

Increasing evidence demonstrates that long non-coding RNAs (lncRNAs) play important regulatory roles in mediating initiation and progression of lung adenocarcinoma (LA), which is one of the most lethal in humans. A previous study reported that lncRNAZXF1 was dysregulated in LA and enhanced expression of ZXF1 promoted the invasion and metastasis in LA. However, the effect of ZXF1 on LA progression and its underlying mechanisms were not thoroughly investigated. In our in vitro experiments, qRT-PCR revealed that the expression level of ZXF1 in LA tissues and tumor cells were significantly higher than that in adjacent normal tissues and normal cells. Furthermore, bioinformatics analysis, luciferase reporter assay, western blot and RNA immunoprecipitation (RIP) assay showed that ZXF1 could directly interact with miR-634, which targets GRB2. Therefore, we propose that ZXF1 could function as an oncogene partly by sponging miR-634 and therefore regulating GRB2 expression in LA. Overall, this study demonstrated, for the first time, that the lncRNA ZXF1/miR-634/GRB2 axis plays crucial roles in modulating LA progression. Moreover, lncRNA ZXF1 might potentially improve LA prognosis and serve as a therapeutic target for the treatment of LA.

scholarly journals Long non-coding RNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression by sponging miR-655-3p

2020 ◽  
Author(s):  
Yuxin Zhao ◽  
Zhaoxia Wang ◽  
Meili Gao ◽  
Xuehong Wang ◽  
Hui Feng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
B Cell Lymphoma ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Western Blot Assay ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Background: Long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was reported as an oncogene in many tumors including retinoblastoma (RB). This research mainly focused on the functions and mechanism of MALAT1 in RB.Methods: The levels of MALAT1, microRNA-655-3p (miR-655-3p), and ATPase family AAA domain containing 2 (ATAD2) in RB tissues and cells were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The cell viability and apoptotic rate were monitored via cell counting kit 8 (CCK8) assay and flow cytometry, respectively. The protein levels of p21, CyclinD1, B-cell lymphoma-2 (Bcl-2), cleaved-casp-3, E-cadherin, Ncadherin, Vimentin, and ATAD2 were detected by Western blot assay. Transwell assay was performed to estimate the abilities of migration and invasion. The interactions between miR-655-3p and MALAT1 or ATAD2 were predicted by starBase. Dual-luciferase reporter assay was constructed to verify these interactions. The mice model experiments were established to validate the effects of MALAT1 in vivo.Results: MALAT1and ATAD2 were significantly increased while the level of miR-655-3p was remarkably decreased in RB tissues and cells. MALAT1 knockdown inhibited cell proliferation, metastasis, and epithelial-mesenchymal transition (EMT) but promoted apoptosis via miR-655-3p in vitro, and blocked xenograft tumor growth in vivo. MALAT1 was validated to sponge miR-655-3p and ATAD2 was verified as a candidate of miR-655-3p. MiR-655-3p overexpression inhibited cell proliferation but promoted apoptosis by targeting ATAD2. MALAT1 silencing affected cell behaviors by regulating ATAD2. MALAT1 depletion down-regulated ATAD2 expression via miR-655-3p in RB cells.Conclusion: MALAT1 positively regulated ATAD2 to accelerate cell proliferation but retard apoptosis by sponging miR-655-3p in RB cells.

scholarly journals Long non-coding RNA CACNA1G-AS1 promotes proliferation and invasion and inhibits apoptosis by regulating expression of miR-205 in human keloid fibroblasts

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Xu Zhao ◽  
Xiang Jie ◽  
Ya-kun Gao ◽  
Bing Nie ◽  
Hua Jiang
Keyword(s):  
Caspase 3 ◽  
Fibrous Tissue ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Non Coding Rna ◽  
Gated Channel ◽  
Competing Endogenous Rnas ◽  
Rna Immunoprecipitation ◽  
Proliferation And Invasion ◽  
Keloid Fibroblasts

Abstract Background: Keloid is a fibrous tissue proliferative disease in which proliferative scars grow beyond the boundary of the original wound skin. Long non-coding RNAs (lncRNAs), as competing endogenous RNAs (ceRNAs), bind to microRNAs (miRNAs) to regulate various biological processes. The present study was aim to illuminate the mechanism of calcium voltage-gated channel subunit alpha1 G antisense RNA 1 (CACNA1G-AS1) in human keloid fibroblasts. Methods: CACNA1G-AS1 and miR-205 levels were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) assay was used to measure the proliferation and transwell assay was performed to evaluate cell invasion. Furthermore, the apoptosis rates of cells were evaluated by flow cytometry analysis, and the activity of caspase-3 in keloid fibroblasts was tested by Caspase-3 activity assay. Dual luciferase reporter assay was carried out to examine the relationship between CACNA1G-AS1 and miR-205 and RNA immunoprecipitation (RIP) assay was conducted to further confirm the relation. Results: CACNA1G-AS1 level was up-regulated in keloid tissues and keloid fibroblasts. CACNA1G-AS1 overexpression promoted proliferation and invasion and suppressed apoptosis of keloid fibroblasts. Moreover, miR-205 was targeted by CACNA1G-AS1 and miR-205 was markedly decreased in keloid tissues and keloid fibroblasts. Also, miR-205 expression was negatively regulated by CACNA1G-AS1 and miR-205 silencing enhanced proliferation and invasion and inhibited apoptosis. Furthermore, CACNA1G-AS1 and miR-205 played the antagonistic role in miR-205 expression, proliferation, invasion, and apoptosis of keloid fibroblasts. Conclusion: CACNA1G-AS1 suppressed miR-205 expression to promote proliferation and invasion and inhibit apoptosis in human keloid fibroblasts.

scholarly journals GAS6-AS1 Overexpression Increases GIMAP6 Expression and Inhibits Lung Adenocarcinoma Progression by Sponging miR-24-3p

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuanyong Wang ◽  
Minge Ma ◽  
Chuan Li ◽  
Yuling Yang ◽  
Maolong Wang
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Non Coding Rna ◽  
Rna Immunoprecipitation ◽  
Reporter Assays ◽  
Potential Interactions ◽  
Long Non Coding Rna

GAS6 antisense RNA 1 (GAS6-AS1) is a long non-coding RNA involved in hepatocellular carcinoma and gastric cancer. However, the functional role of GAS6-AS1 in lung adenocarcinoma (LUAD) remains unclear. In the present study, qRT-PCR was used to measure the levels of GAS6-AS1, GIMAP6 and miR-24-3p expression in LUAD samples and cell lines. CCK-8 and colony formation assays were used to determine cell proliferation. Cell migration and invasion were evaluated using wound healing and transwell assays, respectively. The potential interactions between molecules were assessed using RNA immunoprecipitation and luciferase reporter assays. Western blot analysis was used to quantify protein expression. The anti-tumor effect of over-expressed GAS6-AS1 on LUAD was also examined in vivo in xenograft tumor experiments. The expression of GAS6-AS1 was notably downregulated in LUAD samples and cell lines and associated with a poor prognosis. GAS6-AS1 overexpression inhibited the migration and invasion of A549 and H1650 cells. Down-expressed GAS6-AS1 acted as a sponge for miR-24-3p and down-regulated the expression of its target, GTPase IMAP Family Member 6. These findings suggested that GAS6-AS1 might represent a potential diagnostic biomarker for LUAD.

scholarly journals Long non-coding RNA MALAT1 regulates oxaliplatin-resistance via miR-324-3p/ADAM17 axis in colorectal cancer cells

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Changru Fan ◽  
Qiulan Yuan ◽  
Guifeng Liu ◽  
Yuliang Zhang ◽  
Maojun Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Malignant Tumors ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Western Blot Assay ◽  
Resistance Response ◽  
Non Coding Rna ◽  
Colorectal Cancer Cells ◽  
Long Non Coding Rna

Abstract Background Colorectal cancer (CRC) is one of the most general malignant tumors. Accumulating evidence implied that long non-coding RNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) participated in the tumorigenesis of CRC. However, the effect of MALAT1 in drug-resistance needed to be further illustrated. Methods Levels of MALAT1, microRNA (miR)-324-3p, and a disintegrin and metalloprotease metallopeptidase domain 17 (ADAM17) were detected using quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Cell Counting Kit 8 (CCK-8) was used to assess the half maximal inhibitory concentration (IC50) of oxaliplatin (Ox). Meanwhile, cell proliferation, migration and apoptosis were detected by CCK-8, transwell assay, and flow cytometry, respectively. The interaction between miR-324-3p and MALAT1 or ADAM17 was clarified by dual-luciferase reporter assay. Also, the effect of MALAT1 on tumor growth was detected in xenograft tumor mice treated with Ox. Results Significant up regulation of MALAT1 and ADAM17, and decrease of miR-324-3p were observed in Ox-resistant CRC tissues and cells. MALAT1 deficiency enhanced the sensitivity of Ox-resistant CRC cells response to Ox, while miR-324-3p repression or ADAM17 acceleration could overturn this effect. Moreover, MALAT1 silencing repressed tumor growth in Ox-treated nude mice. Mechanically, MALAT1 exerted promotion effect on the resistance response to Ox via miR-324-3p/ADAM17 axis in Ox-resistant CRC cells. Conclusion MALAT1 modulated the sensitivity of Ox through ADAM17 in Ox-resistant CRC cells by sponging miR-324-3p, thus MALAT1 might serve as a novel insight for the therapy of CRC.

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