scholarly journals Aberrant expression of PROS1 correlates with human papillary thyroid cancer progression

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11813
Author(s):  
Jing Wang ◽  
Minxiang Lei ◽  
Zhijie Xu
Keyword(s):  
Thyroid Cancer ◽  
Cancer Progression ◽  
Biological Significance ◽  
Protein S ◽  
Gene Expression Omnibus ◽  
Papillary Thyroid ◽  
Migration Ability ◽  
Aberrant Expression ◽  
And Migration

Background Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC). Considering the important association between cellular immunity and PTC progression, it is worth exploring the biological significance of immune-related signaling in PTC. Methods Several bioinformatics tools, such as R software, WEB-based Gene SeT AnaLysis Toolkit (WebGestalt), Database for Annotation, Visualization and Integrated Discovery (DAVID), Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape were used to identify the immune-related hub genes in PTC. Furthermore, in vitro experiments were adopted to identify the proliferation and migration ability of PROS1 knockdown groups and control groups in PTC cells. Results The differentially expressed genes (DEGs) of five datasets from Gene Expression Omnibus (GEO) contained 154 upregulated genes and 193 downregulated genes, with Protein S (PROS1) being the only immune-related hub gene. Quantitative real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) have been conducted to prove the high expression of PROS1 in PTC. Moreover, PROS1 expression was significantly correlated with lymph nodes classification. Furthermore, knockdown of PROS1 by shRNAs inhibited the cell proliferation and cell migration in PTC cells. Conclusions The findings unveiled the clinical relevance and significance of PROS1 in PTC and provided potential immune-related biomarkers for PTC development and prognosis.

scholarly journals MicroRNA-29a Promotes Pancreatic Cancer Growth by Inhibiting Tristetraprolin

2015 ◽  
Vol 37 (2) ◽  
pp. 707-718 ◽  
Author(s):  
Xian-Jun Sun ◽  
Bing-Yan Liu ◽  
Shuo Yan ◽  
Ting-Hui Jiang ◽  
Hui-Qin Cheng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Ectopic Expression ◽  
Inflammatory Factors ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
Tumor Tissues ◽  
And Migration

Background/Aims: The microRNA (miR) 29 family has been studied extensively for its involvement in several diseases, and aberrant expression of its members is associated with tumorigenesis and cancer progression. Here, we examined the role of miR-29a in pancreatic cancer and the involvement of tristetraprolin (TTP). Methods: We monitored miR-29a and TTP expression in pancreatic cancer by qRT-PCR and western blotting. The effect of miR-29a on pancreatic cancer was determined through MTT assay and migration assay. The results were validated in the tumorigenesis model. Results: We found that miR-29a was up regulated in pancreatic tumor tissues and cell lines and positively correlated with metastasis. Ectopic expression of miR-29a increased the expression of pro-inflammatory factors and epithelial-mesenchymal transition (EMT) markers, through down regulating TTP. TTP was down regulated in tumor tissues, and its ectopic expression decreased cell viability and migration in vitro, inhibited tumor growth and the EMT phenotype in vivo, and reversed the effect of miR-29a on tumor cell proliferation and invasion in vitro and in vivo. Conclusion: Our results suggest that miR-29a acts as an oncogene by down regulating TTP and provide the basis for further studies exploring the potential of miR-29a and TTP as biomarkers and targets for the treatment of pancreatic cancer.

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 MiR-30c-5p loss-induced PELI1 accumulation regulates cell proliferation and migration via activating PI3K/AKT pathway in papillary thyroid carcinoma

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Tingting Zheng ◽  
Youxing Zhou ◽  
Xiaowei Xu ◽  
Xin Qi ◽  
Jiameng Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Akt Pathway ◽  
Papillary Thyroid ◽  
Aberrant Expression ◽  
Downstream Target ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background The aberrant expression of E3 ubiquitin ligase Pellino-1 (PELI1) contributes to several human cancer development and progression. However, its expression patterns and functional importance in papillary thyroid cancer (PTC) remains unknown. Methods PELI1 expression profiles in PTC tissues were obtained and analyzed through the starBase v3.0 analysis. Real-time PCR, Immunohistochemical assays (IHC) and Western blot were used to investigate the mRNA and protein levels of PELI1 in PTC. The effects of PELI1 on PTC cell progression were evaluated through CCK-8, colony formation, Transwell, and Wound healing assay in vitro, and a PTC xenograft mouse model in vivo. The downstream target signal of PELI1 in PTC was analyzed by using Kyoto encyclopedia of genes and genomes (KEGG), and bioinformatics tools were used to identify potential miRNAs targeting PELI1. Human umbilical cord mesenchymal stem cells were modified by miR-30c-5p and the miR-30c-5p containing extracellular vesicles were collected (miR-30c-5p-EVs) by ultra-high-speed centrifugation method. Then, the effects of miR-30c-5p-EVs on PELI1 expression and PTC progression were evaluated both in vitro and in vivo. Results Both mRNA and protein expression of PELI1 were widely increased in PTC tissues, and overexpression of PELI1 was positively correlated with bigger tumor size and lymph node metastases. PELI1 promoted PTC cell proliferation and migration in vitro. While, PELI1 silencing significantly suppressed PTC growth in vivo accompanied with reduced expression of Ki-67 and matrix metallopeptidase 2 (MMP-2). Mechanistically, PI3K-AKT pathway was identified as the downstream target of PELI1, and mediated the functional influence of PELI1 in PTC cells. Moreover, we found that the expression of miR-30c-5p was inversely correlated with PELI1 in PTC samples and further confirmed that miR-30c-5p was a tumor-suppressive miRNA that directly targeted PELI1 to inhibit PTC cell proliferation and migration. Furthermore, we showed that miR-30c-5p-EVs could effectively downregulate PELI1 expression and suppress the PTC cell growth in vitro and in vivo. Conclusion This study not only supported the first evidence that miR-30c-5p loss-induced PELI1 accumulation facilitated cell proliferation and migration by activating the PI3K-AKT pathway in PTC but also provided novel insights into PTC therapy based on miR-carrying-hUCMSC-EVs.

scholarly journals Long Noncoding RNA CCAL Promotes Papillary Thyroid Cancer Progression by Activation of NOTCH1 Pathway

2018 ◽  
Vol 26 (9) ◽  
pp. 1383-1390 ◽  
Author(s):  
Ying Ye ◽  
Yanan Song ◽  
Juhua Zhuang ◽  
Saifei He ◽  
Jing Ni ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Cancer Progression ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Thyroid Tumor ◽  
Migration And Invasion ◽  
Papillary Thyroid

Long noncoding RNA CCAL has been reported to promote tumor progression in various human cancers, including hepatocellular carcinoma, osteosarcoma, and colorectal cancer. However, the role of CCAL in papillary thyroid cancer remains largely unknown. In the present study, we found that the expression of CCAL was upregulated in papillary thyroid tumor tissues compared to adjacent normal tissues. Moreover, the expression of CCAL was positively related with papillary thyroid cancer severity and TNM stage and predicated poor prognosis. Besides, we found that knockdown of CCAL significantly inhibited papillary thyroid cancer cell proliferation, migration, and invasion in vitro and reduced tumor growth and metastasis in vivo. We found that knockdown of CCAL dramatically decreased the expression of NOTCH1 and suppressed the activation of the NOTCH1 signaling pathway. Furthermore, overexpression of NOTCH1 rescued the proliferation, migration, and invasion in papillary thyroid cancer cells. Taken together, our data indicated that CCAL promoted papillary thyroid cancer development and progression by activation of the NOTCH1 pathway, which provided a new insight on the design of therapeutic targets.

scholarly journals MicroRNA-363-3p downregulation in papillary thyroid cancer inhibits tumor progression by targeting NOB1

2020 ◽  
Vol 69 (1) ◽  
pp. 66-74
Author(s):  
Su Dong ◽  
Shuai Xue ◽  
Yue Sun ◽  
Zhe Han ◽  
Lele Sun ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Tumor Progression ◽  
Papillary Thyroid Cancer ◽  
Cancer Progression ◽  
Migration And Invasion ◽  
Papillary Thyroid ◽  
Thyroid Cells

MicroRNA-363-3 p (miR-363–3 p) has been reported to play a crucial role in tumor development and progression, and function as a tumor suppressor in many types of cancer. In our previous studies, we found that miRNA-363–3 p inhibited papillary thyroid carcinoma (PTC) progression by targeting PIK3CA. Meanwhile, we found that NIN1/RPN12 binding protein 1 (NOB1) was significantly upregulated in thyroid carcinoma tissue and downregulation of NOB1 expression significantly inhibited cell proliferation, migration and invasion in PTC. However, the correlation of NOB1 and miR-363–3 p has not been investigated. Here, we performed bioinformatic analysis to explore miRNA targeting NOB1. We found that NOB1 was a target of miR-363–3 p and miR-363–3 p regulated NOB1 expression at the translational and transcriptional levels by targeting its 3’ untranslated region (3'-UTR). Further, we showed that miR-363–3 p inhibited tumor progression by targeting NOB1 in vitro and in vivo. We found that overexpression miR-363–3 p or silencing NOB1 significantly increased G0/G1-phase and decreased S-phase in the human papillary thyroid cells, which led to a significant delay in cell proliferation, indicating miR-363–3 p and NOB1 are crucial for human papillary thyroid cancer tumorigenesis. Collectively, our data unveil that miR-363–3 p negatively regulates NOB1 activity by reducing its stability. This study provides a new therapeutic target for regulation of NOB1 stability to modulate human papillary thyroid cancer progression.

scholarly journals CircRNA circTIAM1 promotes papillary thyroid cancer progression through the miR-646/HNRNPA1 signaling pathway

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Deguang Zhang ◽  
Li Tao ◽  
Nizheng Xu ◽  
Xiaoxiao Lu ◽  
Jianle Wang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Cancer Progression ◽  
High Throughput Sequencing ◽  
Endocrine Tumor ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Papillary Thyroid

AbstractPapillary thyroid cancer (PTC) is a common endocrine tumor with a rapidly increasing incidence in recent years. Although the majority of PTCs are relatively indolent and have a good prognosis, a certain proportion is highly aggressive with lymphatic metastasis, iodine resistance, and easy recurrence. Circular RNAs (circRNAs) are a class of noncoding RNAs that are linked to a variety of tumor processes in several cancers, including PTC. In the current study, circRNA high-throughput sequencing was performed to identify alterations in circRNA expression levels in PTC tissues. circTIAM1 was then selected because of its increased expression in PTC and association with apoptosis, proliferation, and migration of PTC cells in vitro and in vivo. Mechanistically, circTIAM1 acted as a sponge of microRNA-646 and functioned in PTC by targeting miR-646 and heterogeneous ribonucleoprotein A1. Fluorescence in situ hybridization and dual-luciferase reporter assays further confirmed these connections. Overall, our results reveal an important oncogenic role of circTIAM1 in PTC and may represent a potentially therapeutic target against PTC progression.

scholarly journals Cell division cycle 45 promotes papillary thyroid cancer progression via regulating cell cycle

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770534 ◽  
Author(s):  
Jing Sun ◽  
Run Shi ◽  
Sha Zhao ◽  
Xiaona Li ◽  
Shan Lu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Division ◽  
Papillary Thyroid Cancer ◽  
Cancer Progression ◽  
Biological Significance ◽  
Cell Division Cycle ◽  
The Cancer Genome Atlas ◽  
Papillary Thyroid ◽  
Normal Tissues

Cell division cycle 45 was reported to be overexpressed in some cancer-derived cell lines and was predicted to be a candidate oncogene in cervical cancer. However, the clinical and biological significance of cell division cycle 45 in papillary thyroid cancer has never been investigated. We determined the expression level and clinical significance of cell division cycle 45 using The Cancer Genome Atlas, quantitative real-time polymerase chain reaction, and immunohistochemistry. A great upregulation of cell division cycle 45 was observed in papillary thyroid cancer tissues compared with adjacent normal tissues. Furthermore, overexpression of cell division cycle 45 positively correlates with more advanced clinical characteristics. Silence of cell division cycle 45 suppressed proliferation of papillary thyroid cancer cells via G1-phase arrest and inducing apoptosis. The oncogenic activity of cell division cycle 45 was also confirmed in vivo. In conclusion, cell division cycle 45 may serve as a novel biomarker and a potential therapeutic target for papillary thyroid cancer.

Knockout of Ajuba Attenuates the Growth and Migration of Hepatocellular Carcinoma Cells

2020 ◽  
Vol 160 (11-12) ◽  
pp. 650-658
Author(s):  
Yichen Le ◽  
Yi He ◽  
Meirong Bai ◽  
Ying Wang ◽  
Jiaxue Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Cancer Progression ◽  
Normal Liver ◽  
Cell Growth And Migration ◽  
And Migration ◽  
Hcc Cells

Ajuba has been found to be mutated or aberrantly regulated in several human cancers and plays important roles in cancer progression via different signaling pathways. However, little is known about the role of Ajuba in hepatocellular carcinoma (HCC). Here, we found an upregulation of Ajuba expression in HCC tissues compared with normal liver tissues, while a poor prognosis was observed in HCC patients with high Ajuba expression. Knockout of Ajuba in HCC cells inhibited cell growth in vitro and in vivo, suppressed cell migration, and enhanced the cell apoptosis under stress. Moreover, re-expression of Ajuba in Ajuba-deficient cells could restore the phenotype of Ajuba-deficient cells. In conclusion, these results indicate that Ajuba is upregulated in HCC and promotes cell growth and migration of HCC cells, suggesting that Ajuba could possibly be a new target for HCC diagnosis and treatment.

scholarly journals A 5′-tRNA halve, tiRNA-Gly promotes cell proliferation and migration via binding to RBM17 and inducing alternative splicing in papillary thyroid cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Litao Han ◽  
Hejing Lai ◽  
Yichen Yang ◽  
Jiaqian Hu ◽  
Zhe Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Alternative Splicing ◽  
Papillary Thyroid Cancer ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Papillary Thyroid ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background tRNA-derived small noncoding RNAs (sncRNAs) are mainly categorized into tRNA halves (tiRNAs) and fragments (tRFs). Biological functions of tiRNAs in human solid tumor are attracting more and more attention, but researches concerning the mechanisms in tiRNAs-mediated tumorigenesis are rarely. The direct regulatory relationship between tiRNAs and splicing-related proteins remain elusive. Methods Papillary thyroid carcinoma (PTC) associated tRNA fragments were screened by tRNA fragments deep sequencing and validated by qRT-PCR and Northern Blot in PTC tissues. The biological function of tRNA fragments were assessed by cell counting kit, transwells and subcutaneous transplantation tumor of nude mice. For mechanistic study, tRNA fragments pull-down, RNA immunoprecipitation, Western Blot, Immunofluorescence, Immunohistochemical staining were performed. Results Herein, we have identified a 33 nt tiRNA-Gly significantly increases in papillary thyroid cancer (PTC) based on tRFs & tiRNAs sequencing. The ectopic expression of tiRNA-Gly promotes cell proliferation and migration, whereas down-regulation of tiRNA-Gly exhibits reverse effects. Mechanistic investigations reveal tiRNA-Gly directly bind the UHM domain of a splicing-related RNA-binding protein RBM17. The interaction with tiRNA-Gly could translocate RBM17 from cytoplasm into nucleus. In addition, tiRNA-Gly increases RBM17 protein expression via inhibiting its degradation in a ubiquitin/proteasome-dependent way. Moreover, RBM17 level in tiRNA-Gly high-expressing human PTC tissues is upregulated. In vivo mouse model shows that suppression of tiRNA-Gly decreases RBM17 expression. Importantly, tiRNA-Gly can induce exon 16 splicing of MAP4K4 mRNA leading to phosphorylation of downstream signaling pathway, which is RBM17 dependent. Conclusions Our study firstly illustrates tiRNA-Gly can directly bind to RBM17 and display oncogenic effect via RBM17-mediated alternative splicing. This fully novel model broadens our understanding of molecular mechanism in which tRNA fragment in tumor cells directly bind RNA binding protein and play a role in alternative splicing.

scholarly journals YB-1 Is Altered in Pregnancy-Associated Disorders and Affects Trophoblast in Vitro Properties via Alternation of Multiple Molecular Traits

2021 ◽  
Vol 22 (13) ◽  
pp. 7226
Author(s):  
Violeta Stojanovska ◽  
Aneri Shah ◽  
Katja Woidacki ◽  
Florence Fischer ◽  
Mario Bauer ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Progression ◽  
Cell Function ◽  
Trophoblast Cell ◽  
Mrna Levels ◽  
Trophoblast Cells ◽  
Invasion And Migration ◽  
And Migration ◽  
Apoptosis And Inflammation

Cold shock Y-box binding protein-1 (YB-1) coordinates several molecular processes between the nucleus and the cytoplasm and plays a crucial role in cell function. Moreover, it is involved in cancer progression, invasion, and metastasis. As trophoblast cells share similar characteristics with cancer cells, we hypothesized that YB-1 might also be necessary for trophoblast functionality. In samples of patients with intrauterine growth restriction, YB-1 mRNA levels were decreased, while they were increased in preeclampsia and unchanged in spontaneous abortions when compared to normal pregnant controls. Studies with overexpression and downregulation of YB-1 were performed to assess the key trophoblast processes in two trophoblast cell lines HTR8/SVneo and JEG3. Overexpression of YB-1 or exposure of trophoblast cells to recombinant YB-1 caused enhanced proliferation, while knockdown of YB-1 lead to proliferative disadvantage in JEG3 or HTR8/SVneo cells. The invasion and migration properties were affected at different degrees among the trophoblast cell lines. Trophoblast expression of genes mediating migration, invasion, apoptosis, and inflammation was altered upon YB-1 downregulation. Moreover, IL-6 secretion was excessively increased in HTR8/SVneo. Ultimately, YB-1 directly binds to NF-κB enhancer mark in HTR8/SVneo cells. Our data show that YB-1 protein is important for trophoblast cell functioning and, when downregulated, leads to trophoblast disadvantage that at least in part is mediated by NF-κB.

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