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The role of long non-coding RNA H19 in breast cancer.

ABSTRACT: Breast cancer is the most common malignant tumor in women in the majority of countries, such as China, Britain and Australia, and its morbidity and mortality rates remain very high. Long non-coding RNAs (lncRNAs) are non-coding RNAs (ncRNAs) >200 nucleotides in length that lack open reading frames. LncRNA H19 is a transcription product of the H19 gene, and the aberrant expression of H19 can be demonstrated in various types of tumor cell. The purpose of the present review was to elaborate the role of H19 in breast cancer. H19 can regulate gene expression in breast cancer at multiple levels, including epigenetic, transcriptional and posttranscriptional. The abnormal expression of H19 is closely associated with the tumorigenesis and progression of breast cancer via different underlying molecular mechanisms, such as encoding microRNA-675, competing endogenous RNA regulation and interacting with MYC. A large number of clinical studies have suggested that H19 can serve as a potential biomarker for the diagnosis of breast cancer. High expression levels of H19 increases the drug resistance of breast cancer cells and is associated with poor prognosis within patients with breast cancer. Therefore, serum H19 levels may have momentous significance in the clinical setting.

SUBMITTER: Wang J

PROVIDER: S-EPMC6924119 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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The role of long non-coding RNA H19 in breast cancer.

Wang Ji J Sun Jinyu J Yang Fen F

Oncology letters 20191114 1

Breast cancer is the most common malignant tumor in women in the majority of countries, such as China, Britain and Australia, and its morbidity and mortality rates remain very high. Long non-coding RNAs (lncRNAs) are non-coding RNAs (ncRNAs) >200 nucleotides in length that lack open reading frames. LncRNA H19 is a transcription product of the H19 gene, and the aberrant expression of H19 can be demonstrated in various types of tumor cell. The purpose of the present review was to elaborate the rol ...[more]

PMID: 31897110

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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

The role of long non-coding RNA H19 in breast cancer.

Publications

The role of long non-coding RNA H19 in breast cancer.

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