Dataset Information

Long non-coding RNA H19 promotes TDRG1 expression and cisplatin resistance by sequestering miRNA-106b-5p in seminoma.

ABSTRACT: The role of TDRG1 in tumorigenesis and the progression of seminoma, as well as its role in regulating chemosensitivity of seminoma to cisplatin through the PI3K/Akt/mTOR signaling pathway, has been previously defined. However, the detailed mechanism underlying TDRG1 expression and concomitant chemoresistance conditions are unknown. Furthermore, it has been reported that non-protein-coding RNAs play an important role in a variety of vital processes including cellular chemosensitivity. However, the role of non-protein-coding RNAs in regulating the chemosensitivity of seminoma remains unknown. In this study, using microarray analysis, we found that long non-coding RNA H19 was upregulated while miRNA-106b-5p was downregulated in an established cisplatin-resistant TCam-2 cell line. Moreover, H19 acts as a miRNA-106b-5p sponge and thus impairs the function of miRNA-106b-5p on its target gene, TDRG1. Based on these findings, we propose that H19 promotes the expression of TDRG1 by sequestering miRNA-106b-5p and uses this mechanism to facilitate cell survival in cisplatin-based chemotherapeutic conditions. These findings elucidate the mechanisms, at least partially, applied to deregulate TDRG1 and cisplatin sensitivity, and may provide new therapeutic possibilities for chemoresistant seminoma.

SUBMITTER: Wei J

PROVIDER: S-EPMC6308085 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other

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Long non-coding RNA H19 promotes TDRG1 expression and cisplatin resistance by sequestering miRNA-106b-5p in seminoma.

Wei Jingchao J Gan Yu Y Peng Dongyi D Jiang Xianzhen X Kitazawa Riko R Xiang Yali Y Dai Yingbo Y Tang Yuxin Y Yang Jianfu J

Cancer medicine 20181114 12

The role of TDRG1 in tumorigenesis and the progression of seminoma, as well as its role in regulating chemosensitivity of seminoma to cisplatin through the PI3K/Akt/mTOR signaling pathway, has been previously defined. However, the detailed mechanism underlying TDRG1 expression and concomitant chemoresistance conditions are unknown. Furthermore, it has been reported that non-protein-coding RNAs play an important role in a variety of vital processes including cellular chemosensitivity. However, th ...[more]

PMID: 30430771

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Project description:Advanced gallbladder cancer (GBC) is one of the most malignant of all types of biliary tract cancers that is associated with poor prognosis and high mortality. Accumulating evidence suggest that the B7 family of proteins serve an essential role in various types of cancers, including GBC. However, the potential function and regulatory mechanism of human endogenous retrovirus‑H long terminal repeat‑associating protein 2 (HHLA2; also known as B7‑H7 or B7H5) in GBC remain poorly understood. In the present study, immunohistochemistry was used to examine the expression pattern of HHLA2 in samples from 89 patients with GBC. The possible association between HHLA2 expression and the clinicopathological parameters, including prognosis, were then assessed. Using lentiviruses, overexpression of HHLA2 plasmid or short‑hairpin RNA (shRNA) of HHLA2 were transfected into GBC‑SD cells to overexpress or knock down HHLA2 expression, respectively. The effects of HHLA2 overexpression and knockdown on the epithelial‑mesenchymal transition (EMT) process on GBC‑SD cells were measured by the western blotting and immunofluorescence staining of collagen I, N‑cadherin, E‑cadherin, vimentin and α‑SMA. By contrast, changes in cell proliferation were measured using EdU assay. Cell invasion and migration were assessed using Transwell and wound‑healing assays, respectively. In addition, a xenograft mouse model was established to evaluate the tumorigenic ability of the GBC cell line in vivo after stable transfection with lentivirus for HHLA2 overexpression or shRNA for HHLA2 knockdown. The regulatory relationships among TGF‑β1, long non‑coding RNA (lncRNA) H19 (H19) and HHLA2 were then investigated. The mRNA expression of lncRNA H19 were assessed using reverse transcription‑quantitative PCR, whereas the expression levels of HHLA2 were detected by western blotting and immunofluorescence staining. HHLA2 expression was found to gradually increase as the stages of the GBC samples become more advanced. In addition, the expression level of HHLA2 was calculated to be positively associated with the Nevin stage, American Joint Committee on Cancer stage, tumor invasion and regional lymph node metastasis but was negatively associated with the overall patient survival (OS). In vitro experiments demonstrated that overexpression of HHLA2 promoted GBC migration, invasion, proliferation and EMT, whereas in vivo experiments found a promoting role of HHLA2 overexpression on GBC tumor growth. After transfection with lentiviruses encoding the overexpression plasmid of lncRNA H19, GBC migration, invasion, proliferation and EMT were increased. By contrast, knocking down HHLA2 expression suppressed TGF‑β1‑ or lncRNA H19 overexpression‑induced GBC migration, invasion, proliferation and EMT. In addition, HHLA2 knockdown significantly reduced the sizes of the GBC tumors in vivo. These results suggest that HHLA2 overexpression can promote GBC progression. Conversely, ablation of HHLA2 expression inhibited both TGF‑β1‑ and lncRNA H19‑induced GBC progression, suggesting that HHLA2 is a potential therapeutic target for this disease.

Dataset Information

Long non-coding RNA H19 promotes TDRG1 expression and cisplatin resistance by sequestering miRNA-106b-5p in seminoma.

Publications

Long non-coding RNA H19 promotes TDRG1 expression and cisplatin resistance by sequestering miRNA-106b-5p in seminoma.

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