scholarly journals LncRNA PROX1-AS1 promotes proliferation, invasion, and migration in papillary thyroid carcinoma

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Yanyan Shen ◽  
Erjie Xia ◽  
Adheesh Bhandari ◽  
Xiaohui Wang ◽  
Guilong Guo

Evidence has been provided that long noncoding RNAs (LncRNAs) play major roles in affecting essential physiological processes, and many of which seem to have functional roles in tumorigenesis and progression. However, the intrinsic molecular mechanism of LncRNAs acting on papillary thyroid carcinoma is not well understood. In the present study, we found that PROX1-AS1 levels were obviously increased in thyroid cancer cells compared with the normal thyroid epithelial cells. Knockdown of PROX1-AS1 gene expression by siRNA could inhibit cell proliferation. Subsequently, we also observed that silencing PROX1-AS1 might inhibit invasion and migration of thyroid cancer cell lines via modulating the expression of epithelial–mesenchymal transition related proteins. In conclusion, our study indicated that LncRNA PROX1-AS1 could promote papillary thyroid carcinoma development and might serve as a potential targeting marker for papillary thyroid carcinoma.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Weilin Pu ◽  
Xiao Shi ◽  
Pengcheng Yu ◽  
Meiying Zhang ◽  
Zhiyan Liu ◽  
...  

AbstractThe tumor ecosystem of papillary thyroid carcinoma (PTC) is poorly characterized. Using single-cell RNA sequencing, we profile transcriptomes of 158,577 cells from 11 patients’ paratumors, localized/advanced tumors, initially-treated/recurrent lymph nodes and radioactive iodine (RAI)-refractory distant metastases, covering comprehensive clinical courses of PTC. Our data identifies a “cancer-primed” premalignant thyrocyte population with normal morphology but altered transcriptomes. Along the developmental trajectory, we also discover three phenotypes of malignant thyrocytes (follicular-like, partial-epithelial-mesenchymal-transition-like, dedifferentiation-like), whose composition shapes bulk molecular subtypes, tumor characteristics and RAI responses. Furthermore, we uncover a distinct BRAF-like-B subtype with predominant dedifferentiation-like thyrocytes, enriched cancer-associated fibroblasts, worse prognosis and promising prospect of immunotherapy. Moreover, potential vascular-immune crosstalk in PTC provides theoretical basis for combined anti-angiogenic and immunotherapy. Together, our findings provide insight into the PTC ecosystem that suggests potential prognostic and therapeutic implications.


Author(s):  
Dumitru A Iacobas

Publically available (own) transcriptomic data were re-analyzed to quantify the alteration of functional pathways in the thyroid cancer, establish the gene hierarchy, identify potential gene targets and predict the effects of their manipulation. The expression data were generated from one case of papillary thyroid carcinoma (PTC) and from genetically manipulated BCPAP (papillary) and 8505C (anaplastic) human thyroid cancer cell lines. The study used the genomic fabric perspective that considers the transcriptome as a multi-dimensional mathematical object based on the three independent characteristics that can be derived for each gene from the expression data. We found remarkable remodeling of the thyroid hormone synthesis, cell cycle, oxidative phosphorylation and apoptosis pathways. Serine peptidase inhibitor, Kunitz type, 2 (SPINT2) was identified as the Gene Master Regulator of the investigated PTC. The substantial increase of the expression synergism of SPINT2 with apoptosis genes in the cancer nodule with respect to the surrounding normal tissue (NOR) suggests that its experimental overexpression may force the PTC cells into apoptosis with negligible effect on the NOR cells. The predictive value of the expression coordination for the expression regulation was validated with data from 8505C and BCPAP cells before and after lentiviral transfection with DDX19B.


Author(s):  
Wei Zhang ◽  
Ting Liu ◽  
Tianshu Li ◽  
Xudong Zhao

Abstract As important modulators in various physiological processes, circular RNAs (circRNAs) have been increasingly demonstrated in tumors, including papillary thyroid cancer (PTC). Hsa_circRNA_102002 (circ_102002) is a circRNA derived from alternative splicing of ubiquitin-specific peptidase 22 (USP22) transcript, the role of which needs further investigation. Our results suggested the upregulation of circ_102002 in PTC tissues and cells, and its promoting effects on epithelial–mesenchymal transition (EMT) and cell migration. Mechanism studies showed that circ_102002 could sponge microRNA-488-3p (miR-488-3p) and downregulate its expression. The target relationship between miR-488-3p and hyaluronic acid synthetase 2 (HAS2) in PTC was systematically studied. In addition, our results showed that HAS2 overexpression could restore the inhibited cell EMT and migration. Moreover, the inhibitory effect of downregulation of circ_102002 on PTC growth was evaluated in a mouse xenograft model, which involved miR-488-3p and HAS2 regulation. These findings about the signal axis of circ_102002/miR-488-3p/HAS2 may further elucidate the PTC pathogenesis and improve clinical treatment.


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