scholarly journals MicroRNA-205 affects mouse granulosa cell apoptosis and estradiol synthesis by targeting CREB1

2018 ◽  
Author(s):  
Pengju Zhang ◽  
Jun Wang ◽  
Hongyan Lang ◽  
Weixia Wang ◽  
Xiaohui Liu ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Follicular Development ◽  
Luciferase Reporter ◽  
Follicular Atresia ◽  
Qrt Pcr ◽  
Reporter Assays ◽  
Cyclic Amp Response Element ◽  
Cytochrome P450 Family ◽  
Estradiol Synthesis

ABSTRACTMicroRNAs-205 (miR-205), were reportedly to be involved in various physiological and pathological processes, but its biological function in follicular atresia remain unknown. In this study, we investigated the expression of miR-205 in mouse granulosa cells (mGCs), and explored its functions in primary mGCs using a serial of in vitro experiments. The result of qRT-PCR demonstrated that miR-205 expression was significantly increased in early atretic follicles (EAF), and progressively atretic follicles (PAF) compared to healthy follicles (HF). Our results also revealed that overexpression of miR-205 in mGCs significantly promoted apoptosis, caspas-3/9 activities, and inhibited estrogen E2 release, and cytochrome P450 family 19 subfamily A polypeptide 1 (CYP19A1, a key gene in E2 production) expression. Bioinformatics and luciferase reporter assays revealed that the gene of cyclic AMP response element (CRE)-binding protein 1 (CREB1) was a potential target of miR-205. qRT-PCR and western blot assays revealed that overexpression of miR-205 inhibited the expression of CREB1 in mGCs. Importantly, CREB1 upregulation partially rescued the effects of miR-205 on apoptosis, caspase-3/9 activities, E2 production and CYP19A1 expression in mGCs. Our results indicate that miR-205 may play an important role in ovarian follicular development and provide new insights into follicular atresia.

scholarly journals Long noncoding RNA HOTAIR mediates the estrogen-induced metastasis of endometrial cancer cells via the miR-646/NPM1 axis

2018 ◽  
Vol 314 (6) ◽  
pp. C690-C701 ◽  
Author(s):  
Yun-xiao Zhou ◽  
Chuan Wang ◽  
Li-wei Mao ◽  
Yan-li Wang ◽  
Li-qun Xia ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Qrt Pcr ◽  
Reporter Assays ◽  
Ec Cells

LncRNA homeobox (HOX) transcript antisense intergenic RNA (HOTAIR) has been confirmed to be involved in the tumorigenic progression of endometrial carcinoma (EC). However, the molecular mechanisms of HOTAIR in EC are not fully elucidated. The expression of HOTAIR and miR-646 in human EC tissues was determined by qRT-PCR. The effect of miR-646 on EC cells was assessed by the cell viability, migration, and invasion using CCK-8 assays and transwell assays. RNA-binding protein immunoprecipitation assays and RNA pull-down assays were performed to explore the interaction between HOTAIR and miR-646. The regulation of miR-646 on nucleophosmin 1 (NPM1) was tested using luciferase reporter assays. MiR-646 expression was significantly decreased both in human EC tissues ( n = 23) and cell lines (Ishikawa and HEC-1-A) compared with the control. Moreover, miR-646 expression was negatively related to HOTAIR in human EC tissues ( n = 23). Our results also showed that miR-646 overexpression considerably attenuated the E2-promoted viability, migration, and invasion of Ishikawa and HEC-1-A cells in vitro. In addition, HOTAIR was confirmed to regulate the viability, migration, and invasion of EC cells through negative regulating miR-646. More importantly, we also demonstrated that NPM1 was the target of miR-646, and HOTAIR promoted NPM1 expression through interacting with miR-646 in EC cells. Taken together, our findings presented that HOTAIR could regulate NPM1 via interacting with miR-646, thereby governing the viability, migration, and invasion of EC cells.

Molecular Mechanism of circRAPGEF5 in Regulating the Molecular Axis of microRNA-4712-5p/Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Epsilon Affecting Cellular Proliferation and Apoptosis in Mammary Cancer

2021 ◽  
Vol 11 (6) ◽  
pp. 1053-1058
Author(s):  
Tao Chen ◽  
Shengrong Sun
Keyword(s):  
Western Blot ◽  
Cancer Cells ◽  
Mammary Cancer ◽  
Caspase 3 ◽  
Cellular Proliferation ◽  
Molecular Axis ◽  
Luciferase Reporter ◽  
Qrt Pcr ◽  
Proliferation And Apoptosis ◽  
Reporter Assays

To understand the molecular mechanism of circRAPGEF5, its effect on the proliferation and apoptosis of mammary cancer cells, and its regulatory effect on the molecular axis of miRNA-4712-5p/YWHAE. qRT-PCR and Western blot were used to test circRAPGEF5, miRNA-4712-5p, and YWHAE expression in mammary cancer and paracancerous tissues. The human mammary cancer cell, MDA-MB-231, was cultured in vitro, and pcDNA-NC, pcDNA-circRAPGEF5, anti-miRNA-NC, anti-miRNA-4712-5p, pcDNA-circRAPGEF5, and miRNA-NC, pcDNA-circRAPGEF5 were transfected into MDA-MB-231 cells with miRNA-4712-5p mimics. qRT-PCR and Western blot were employed to detect circRAPGEF5, miRNA-4712-5p, and YWHAE expression in cells. The CCK-8 methodand plate clone formation experiment were conducted to test cellular proliferation ability. Flow cytometry was performed to detect apoptosis rate. Dual luciferase reporter assays were used to test the targeting association between circRAPGEF5 and miRNA-4712-5p, and the targeting association between miRNA-4712-5p and YWHAE. Western blot was utilized to detect Bcl-2, Bax, and Cleared Caspase-3 protein expression. In comparison with paracancerous tissues, circRAPGEF5 and YWHAE expression levels in mammary cancer tissues were significantly reduced (P < 0.05), and miRNA-4712-5p expression levels were significantly increased (P < 0.05). Transfection of pcDNA-circRAPGEF5 or trans-anti-miRNA-4712-5p could reduce the optical density (OD) value, Bcl-2 protein level and clonal formation number to a significant extent (P < 0.05), and it increases Bax and Cleaved Caspase-3 apoptosis rate and protein levels (P < 0.05). Dual luciferase reporter assays confirmed that there was target binding between circRAPGEF5 and miRNA-4712-5p and between miRNA-4712-5p and YWHAE. Co-transfection of pcDNA-circRAP GEF5 and miRNA-4712-5p could greatly reduce transfection of pcDNA-circRAP GEF5 and its effect on the proliferation and apoptosis of MDA-MB-231 cells. Overexpression of circRAPGEF5 can inhibit the proliferation of mammary cancer cells and induce apoptosis by regulating the molecular axis of miRNA-4712-5p/YWHAE.

scholarly journals GAS5 Regulates RECK Expression and Inhibits Invasion Potential of HCC Cells by Sponging miR-135b

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Liang Yang ◽  
Jianshuai Jiang
Keyword(s):  
Tumor Suppressor ◽  
Noncoding Rna ◽  
Luciferase Reporter ◽  
Tissue Samples ◽  
Qrt Pcr ◽  
Promising Therapeutic Target ◽  
Reporter Assays ◽  
Proliferation And Metastasis ◽  
Cell Proliferation And Metastasis

Objectives. Long noncoding RNA (LncRNA) growth arrest-specific 5 (GAS5) has been characterized as a tumor suppressor in numerous kinds of human cancers. Its anticancer function in hepatocellular carcinoma (HCC) includes repression of cell proliferation and metastasis, leaving the internal mechanisms unclear. In this study, we intended to examine the anti-invasion effects of GAS5 on HCC and explore the downstream regulatory mechanisms.Methods. Expression of GAS5 and microRNA-135b (miR-135b) was analyzed by qRT-PCR in paired HCC tissue samples. Their correlation with HCC patients’ survival was determined. Transwell assays were done to evaluatein vitroinvasion ability. Targeting of GAS5 and RECK by miR-135b was confirmed by qRT-PCR, western blot, and luciferase reporter assays.Results. Decreased GAS5 and increased miR-135b in HCC inversely correlate with each other and both correlate with poor prognosis of HCC patients. Functionally, GAS5 suppresses while miR-135b promotes HCC cell invasion capacitiesin vitro. Mechanistically, GAS5 is a target of miR-135b. Furthermore, GAS5 positively regulates expression of RECK, also a target of miR-135b, which further inhibits MMP-2 expression and contributes to invasion repression.Conclusion. GAS5 acted as a tumor suppressor in HCC invasion in a competing endogenous RNA manner. Our findings indicate that GAS5 is a promising therapeutic target for HCC treatment.

scholarly journals MiR-214-3p Promotes Proliferation and Inhibits Estradiol Synthesis In Porcine Granulosa Cells

2020 ◽  
Author(s):  
Shengjie Shi ◽  
Xiaoge Zhou ◽  
Jingjing Li ◽  
Lutong Zhang ◽  
Yamei Hu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cytochrome P450 ◽  
Granulosa Cells ◽  
Follicular Development ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Cell Cycle Protein ◽  
Porcine Granulosa Cells ◽  
Cytochrome P450 Family ◽  
Estradiol Synthesis

Abstract Background: Granulosa cells proliferation and estradiol synthesis significantly affect follicular development. The miR-214-3p expression in the ovarian tissues of high-yielding sows is higher than that in low-yielding sows, indicating that miR-214-3p may be involved in sow fertility. However, the functions and mechanisms of miR-214-3p on granulosa cells are unclear. In this study, miR-214-3p was transfected into porcine ovarian granulosa cells to investigate its functions in terms of proliferation and estradiol synthesis via flow cytometry, CCK-8 assay, EdU staining, ElisA, Real-Time PCR, and Western blot analyses. We also identified the targets of miR-214-3p via Luciferase Reporter Assay. Results: Our findings revealed that miR-214-3p promotes proliferation and inhibits estradiol synthesis in porcine granulosa cells. We also found that miR-214-3p up-regulates the expression of cell cycle genes including Cell cycle protein B (Cyclin B), Cell cycle protein D (Cyclin D), Cell cycle protein E (Cyclin E), and Cyclin-dependent kinase 4 (CDK4) at the transcription and translation levels, while down-regulating the mRNA and protein levels of cytochrome P450 family 11 subfamily A member 1 (CYP11A1), cytochrome P450 family 19 subfamily A member 1 (CYP19A1), and steroidogenic acute regulatory protein (StAR) (i.e., the key enzymes in estradiol synthesis). On-line prediction, bioinformatics analysis, a luciferase reporter assay, RT-qPCR, and Western blot results showed that the target genes of miR-214-3p in proliferation and estradiol synthesis are Mfn2 and NR5A1, respectively. Conclusions: Our findings suggest that miR-214-3p plays an important role in the functional regulation of porcine granulosa cells and therefore may be a target gene for regulating follicular development.

scholarly journals E2F1-mediated repression of WNT5A expression Promotes Brain Metastasis Dependent on the ERK1/2 pathway in EGFR-Mutant Non-Small Cell Lung Cancer

2020 ◽  
Author(s):  
Huanhuan Li ◽  
Fan Tong ◽  
Rui Meng ◽  
Ling Peng ◽  
Ruiguang Zhang ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Egfr Mutation ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Qrt Pcr ◽  
Reporter Assays ◽  
Egfr Mutant ◽  
Mutant Cells

Abstract Background: Brain metastasis (BM) is associated with poor prognosis in patients with advanced non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutation reportedly enhances the development of BM. However, the exact mechanism of how EGFR-mutant NSCLC contributes to BM remains unknown. This study was aimed at exploring the mechanism of BM development in EGFR-mutant NSCLC.Methods: WNT5A, was identified by analyzing RNA sequencing data of BM tissue from NSCLC. The expression of WNT5A in NSCLC plasma (n=94) and cells were detected by quantitative real-time PCR (qRT-PCR) and western blotting. WNT5A functions were examined by cell viability, migration, invasion, and immunohistochemistry assay in vitro. A xenograft nude mouse model and BM model were used to observe tumor growth and brain metastasis in vivo. The potential transcription factor of WNT5A was explored using bioinformatics analysis and verified by chromatin immunoprecipitation (ChIP) and luciferase reporter assays. WNT5A targets in NSCLC cells were confirmed using luciferase reporter assay, qRT-PCR, and western blotting.Results: WNT5A was downregulated in BM tissues and EGFR-mutant samples and cells. The overexpression of WNT5A inhibited the growth, migration, and invasion of EGFR-mutant cells in vitro and retarded tumor growth and metastasis in vivo compared to the EGFR wide-type cells. ChIP and luciferase reporter assays showed that E2F1 negatively regulated WNT5A at transcriptional levels, which was suppressed by ERK1/2 inhibitor (U0126) in EGFR-mutant cells. Furthermore, WNT5A inhibited β-catenin activity and the transcriptional levels of its downstream genes in cancer progression.Conclusions: Our research revealed the role of WNT5A in NSCLC BM with EGFR mutation and proved that E2F1-mediated repression of WNT5A was dependent on the ERK1/2 pathway, supporting the notion that targeting the ERK1/2-E2F1-WNT5A pathway could be an effective strategy for treating BM in EGFR-mutant NSCLC.

scholarly journals MicroRNA-195 Activates Hepatic Stellate Cells In Vitro by Targeting Smad7

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Li-Ying Song ◽  
Yu-Tao Ma ◽  
Cui-Fang Wu ◽  
Chun-Jiang Wang ◽  
Wei-Jin Fang ◽  
...  
Keyword(s):  
Hepatic Stellate Cells ◽  
Luciferase Activity ◽  
Stellate Cells ◽  
Luciferase Reporter ◽  
Reporter Plasmid ◽  
Smad Pathway ◽  
Qrt Pcr ◽  
Reporter Assays

Background and Aim. Aberrant activation of the TGF-β1/Smad pathway contributes to the activation of hepatic stellate cells (HSCs). MicroRNA-195 has been shown to regulate the activation of HSCs. The aim of this study was to investigate the role of miRNA-195 in HSCs activation. Methods. A liver fibrotic rat model induced by diethylnitrosamine was established. Dual luciferase reporter assays were performed to verify that Smad7 was the target of miRNA-195. The expression levels of miR-195, Smad7, and α-SMA in HSC-T6 transfected, respectively, with miR-195 mimic, inhibitor, or control were measured by qRT-PCR. The protein expression of Smad7 was detected by Western blot analysis. Results. Enhanced miR-195 and decreased Smad7 were observed in diethylnitrosamine-induced liver fibrotic rats (P<0.05). Dual luciferase reporter assays showed that the miR-195 mimic significantly suppressed the luciferase activity of a reporter plasmid carrying the binding site of miR-195 on the 3′UTR of Smad7 (P<0.05). The miR-195 mimics activated HSCs, further elevated miR-195 and α-SMA (P<0.01), and reduced the Smad7 level (P<0.05). The miR-195 inhibitors blocked the activation of HSCs, reduced the expression of miR-195 and α-SMA (P<0.01), and upregulated the expression of Smad7 (P<0.05). Conclusion. Collectively, we demonstrated that miRNA-195 activated HSCs by targeting Smad7.

scholarly journals MiR-214-3p promotes proliferation and inhibits estradiol synthesis in porcine granulosa cells

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shengjie Shi ◽  
Xiaoge Zhou ◽  
Jingjing Li ◽  
Lutong Zhang ◽  
Yamei Hu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cytochrome P450 ◽  
Granulosa Cells ◽  
Target Genes ◽  
Regulatory Protein ◽  
Follicular Development ◽  
Luciferase Reporter ◽  
Cell Cycle Protein ◽  
Cytochrome P450 Family ◽  
Estradiol Synthesis

Abstract Background Granulosa cells (GCs) proliferation and estradiol synthesis significantly affect follicular development. The miR-214-3p expression in the ovarian tissues of high-yielding sows is higher than that in low-yielding sows, indicating that miR-214-3p may be involved in sow fertility. However, the functions and mechanisms of miR-214-3p on GCs are unclear. This study focuses on miR-214-3p in terms of the effects on GCs proliferation and estradiol synthesis. Results Our findings revealed that miR-214-3p promotes proliferation and inhibits estradiol synthesis in porcine GCs. MiR-214-3p can increase the percentage of S-phase cells, the number of EdU labeled positive cells, and cell viability. However, E2 concentration was reduced after miR-214-3p agomir treatment. We also found that miR-214-3p up-regulates the expression of cell cycle genes including cell cycle protein B (Cyclin B), cell cycle protein D (Cyclin D), cell cycle protein E (Cyclin E), and cyclin-dependent kinase 4 (CDK4) at the transcription and translation levels, but down-regulates the mRNA and protein levels of cytochrome P450 family 11 subfamily A member 1 (CYP11A1), cytochrome P450 family 19 subfamily A member 1 (CYP19A1), and steroidogenic acute regulatory protein (StAR) (i.e., the key enzymes in estradiol synthesis). On-line prediction, bioinformatics analysis, a luciferase reporter assay, RT-qPCR, and Western blot results showed that the target genes of miR-214-3p in proliferation and estradiol synthesis are Mfn2 and NR5A1, respectively. Conclusions Our findings suggest that miR-214-3p plays an important role in the functional regulation of porcine GCs and therefore may be a target gene for regulating follicular development.

scholarly journals LncRNA HAS2-AS1 Promotes Glioblastoma Proliferation by Sponging miR-137

2021 ◽  
Vol 11 ◽  
Author(s):  
Yalin Lu ◽  
Gaochao Guo ◽  
Rujun Hong ◽  
Xingjie Chen ◽  
Yan Sun ◽  
...  
Keyword(s):  
Underlying Mechanism ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Tumor Type ◽  
Downstream Target ◽  
Qrt Pcr ◽  
Lysine Specific Demethylase ◽  
Reporter Assays

GBM (Glioblastoma multiform) is the most malignant tumor type of the central nervous system and has poor diagnostic and clinical outcomes. LncRNAs (Long non-coding RNAs) have been reported to participate in multiple biological and pathological processes, but their underlying mechanism remains poorly understood. Here, we aimed to explore the role of the lncRNA HAS2-AS1 (HAS2 antisense RNA 1) in GBM. GSE103227 was analyzed, and qRT-PCR was performed to measure the expression of HAS2-AS1 in GBM. FISH (Fluorescence in situ hybridization) was performed to verify the localization of HAS2-AS1. The interaction between HAS2-AS1 and miR-137 (microRNA-137) was predicted by LncBook and miRcode followed by dual‐luciferase reporter assays, and the relationships among HAS2-AS1, miR-137 and LSD1 (lysine-specific demethylase 1) were assessed by WB (western blot) and qRT-PCR. Colony formation and CCK-8 (cell counting kit-8) assays were performed as functional tests. In vivo, nude mice were used to confirm the function of HAS2-AS1. HAS2-AS1 expression was upregulated in GBM cell lines, and HAS2-AS1 was localized mainly in the cytoplasm. In vitro, high HAS2-AS1 expression promoted proliferation, and knockdown of HAS2-AS1 significantly inhibited proliferation. Furthermore, HAS2-AS1 functioned as a ceRNA (competing endogenous RNA) of miR-137, leading to the disinhibition of its downstream target LSD1. The miR-137 level was downregulated by HAS2-AS1 overexpression and upregulated by HAS2-AS1 knockdown. In a subsequent study, LSD1 expression was negatively regulated by miR-137, while miR-137 reversed the LSD1 expression levels caused by HAS2-AS1. These results were further supported by the nude mouse tumorigenesis experiment; compared with xenografts with high HAS2-AS1 expression, the group with low levels of HAS2-AS1 exhibited suppressed proliferation and better survival. We conclude that lncRNA HAS2-AS1 promotes proliferation by functioning as a miR‐137 decoy to increase LSD1 levels and thus might be a possible biomarker for GBM.

scholarly journals miR-146a-5p Promotes Chondrocyte Apoptosis and Inhibits Autophagy of Osteoarthritis by Targeting NUMB

Cartilage ◽  
2021 ◽  
pp. 194760352110235
Author(s):  
Hongjun Zhang ◽  
Wendi Zheng ◽  
Du Li ◽  
Jia Zheng
Keyword(s):  
Caspase 3 ◽  
Cartilage Tissue ◽  
Luciferase Reporter ◽  
Chondrocyte Apoptosis ◽  
Knee Cartilage ◽  
Before And After ◽  
Related Proteins ◽  
Human And Mouse

Objective miR-146a-5p was found to be significantly upregulated in cartilage tissue of patients with osteoarthritis (OA). NUMB was shown to be involved in the autophagy regulation process of cells. We aimed to learn whether NUMB was involved in the apoptosis or autophagy process of chondrocytes in OA and related with miR-146a-5p. Methods QRT-PCR was used to detect miR-146a-5p level in 22 OA cartilage tissues and 22 controls. The targets of miR-146a-5p were analyzed using software and the luciferase reporter experiment. The apoptosis and autophagy, and related proteins were detected in chondrocytes treated with miR-146a-5p mimic/inhibitor or pcDNA3.1-NUMB/si-NUMB and IL-1β, respectively. In vivo experiment, intra-articular injection of miR-146a-5p antagomir/NC was administered at the knee of OA male mice before and after model construction. Chondrocyte apoptosis and the expression of apoptosis and autophagy-related proteins were also detected. Results miR-146a-5p was highly expressed in knee cartilage tissue of patients with OA, while NUMB was lowly expressed and negatively regulated by miR-146a-5p. Upregulation of miR-146a-5p can promote cell apoptosis and reduce autophagy of human and mouse chondrocytes by modulating the levels of cleaved caspase-3, cleaved PARP, Bax, Beclin 1, ATG5, p62, LC3-I, and LC3-II. Increasing the low level of NUMB reversed the effects of miR-146a-5p on chondrocyte apoptosis and autophagy. Intra-articular injection of miR-146a-5p antagomir can also reverse the effects of miR-146a-5p on the apoptosis and autophagy of knee joint chondrocytes in OA mice. Conclusion Downregulation of miR-146a-5p suppresses the apoptosis and promotes autophagy of chondrocytes by targeting NUMB in vivo and in vitro.

scholarly journals METTL14 promotes tumorigenesis by regulating lncRNA OIP5-AS1/miR-98/ADAMTS8 signaling in papillary thyroid cancer

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Xiaoping Zhang ◽  
Dan Li ◽  
Chengyou Jia ◽  
Haidong Cai ◽  
Zhongwei Lv ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Papillary Thyroid ◽  
Qrt Pcr ◽  
The Relationship

Abstract Background Papillary thyroid cancer (PTC) is the most common type of cancer of the endocrine system. Long noncoding RNAs (lncRNAs) are emerging as a novel class of gene expression regulators associated with tumorigenesis. Through preexisting databases available for differentially expressed lncRNAs in PTC, we uncovered that lncRNA OIP5-AS1 was significantly upregulated in PTC tissues. However, the function and the underlying mechanism of OIP5-AS1 in PTC are poorly understood. Methods Expression of lncRNA OIP5-AS1 and miR-98 in PTC tissue and cells were measured by quantitative real-time PCR (qRT-PCR). And expression of METTL14 and ADAMTS8 in PTC tissue and cells were measured by qRT-PCR and western blot. The biological functions of METTL14, OIP5-AS1, and ADAMTS8 were examined using MTT, colony formation, transwell, and wound healing assays in PTC cells. The relationship between METTL14 and OIP5-AS1 were evaluated using RNA immunoprecipitation (RIP) and RNA pull down assay. And the relationship between miR-98 and ADAMTS8 were examined by luciferase reporter assay. For in vivo experiments, a xenograft model was used to investigate the effects of OIP5-AS1 and ADAMTS8 in PTC. Results Functional validation revealed that OIP5-AS1 overexpression promotes PTC cell proliferation, migration/invasion in vitro and in vivo, while OIP5-AS1 knockdown shows an opposite effect. Mechanistically, OIP5-AS1 acts as a target of miR-98, which activates ADAMTS8. OIP5-AS1 promotes PTC cell progression through miR-98/ADAMTS8 and EGFR, MEK/ERK pathways. Furthermore, RIP and RNA pull down assays identified OIP5-AS1 as the downstream target of METTL14. Overexpression of METTL14 suppresses PTC cell proliferation and migration/invasion through inhibiting OIP5-AS1 expression and regulating EGFR, MEK/ERK pathways. Conclusions Collectively, our findings demonstrate that OIP5-AS1 is a METTL14-regulated lncRNA that plays an important role in PTC progression and offers new insights into the regulatory mechanisms underlying PTC development.

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