scholarly journals Ang1/Tie2 induces cell proliferation and migration in human papillary thyroid carcinoma via the PI3K/AKT pathway

2017 ◽  
Author(s):  
Ke Ye ◽  
Jindong Li ◽  
Xinying Li ◽  
Shi Chang ◽  
Zhejia Zhang
Keyword(s):  
Cell Proliferation ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Akt Pathway ◽  
Papillary Thyroid ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Chaperone-mediated Autophagy Governs Progression of Papillary Thyroid Carcinoma via PPARγ-SDF1/CXCR4 Signaling

2020 ◽  
Vol 105 (10) ◽  
pp. 3308-3323
Author(s):  
Hong Zhou ◽  
Xin Xie ◽  
Ying Chen ◽  
Yi Lin ◽  
Zhaogen Cai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Papillary Thyroid Carcinoma ◽  
Tumor Cell Proliferation ◽  
Papillary Thyroid ◽  
Cxcr4 Signaling ◽  
Cell Proliferation And Migration ◽  
Underlying Mechanisms ◽  
And Migration ◽  
Chaperone Mediated Autophagy ◽  
Proliferation And Migration

Abstract Context Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Chaperone-mediated autophagy (CMA), 1 type of autophagy, is thought to promote or suppress cancer development in different cancer types. However, the effect of CMA on PTC development and the underlying mechanisms remain unknown. Objective To determine whether CMA plays implied critical roles in the development of PTC. Design We investigated the association between CMA and PTC development in PTC tissues and normal thyroid tissues by detecting the key protein of CMA, lysosome-associated membrane protein type 2A (LAMP2A), using quantitative polymerase chain reaction (PCR) and immunohistochemistry, which were further validated in the TGCA dataset. The effect of CMA on PTC development was studied by cell proliferation, migration, and apoptosis assays. The underlying mechanisms of peroxisome proliferator-activated receptor γ (PPARγ)-stromal cell-derived factor 1 (SDF1)/ C-X-C motif chemokine receptor 4 (CXCR4) signaling were clarified by western blotting, quantitative PCR, and rescue experiments. Knockdown and tamoxifen were used to analyze the effect of estrogen receptor (ER) α on CMA. Results Our study confirmed that CMA, indicated by LAMP2A expression, was significantly increased in PTC tumor tissues and cell lines, and was associated with tumor size and lymph node metastasis of patients. Higher CMA in PTC promoted tumor cell proliferation and migration, thereby promoting tumor growth and metastasis. These effects of CMA on PTC were exerted by decreasing PPARγ protein expression to enhance SDF1 and CXCR4 expression. Furthermore, CMA was found positively regulated by ERα signaling in PTC. Conclusion Our investigation identified CMA regulated by ERα promoting PTC tumor progression that enhanced tumor cell proliferation and migration by targeting PPARγ-SDF1/CXCR4 signaling, representing a potential target for treatment of PTC.

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 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 EGCG inhibited bladder cancer T24 and 5637 cell proliferation and migration via PI3K/AKT pathway

Oncotarget ◽  
2018 ◽  
Vol 9 (15) ◽  
pp. 12261-12272 ◽  
Author(s):  
Ke-Wang Luo ◽  
Wing-Yin Lung ◽  
Chun-Xie ◽  
Xin-Le Luo ◽  
Wei-Ren Huang
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Akt Pathway ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration
Sign in / Sign up

Export Citation Format

Share Document