LncRNA H19 Influences Cellular Activities via the miR-454-3p/BHLHE40 Axis in Anaplastic Thyroid Carcinoma
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Updated: Jul 9, 2025

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Yang Wu1, Jihua Yang2, Honglai Zhang3
1Department of General Surgery (Thyroid Gland/Blood Vessel), The First People's Hospital of Neijiang, Neijiang, China.
Abstract:
Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy threatening patients' life quality. Our previous study has demonstrated that inhibition of long non-coding RNA H19 (lncRNA h19; H19) blocks ATC growth and metastasis. The current study aimed to further explore the potential mechanism of H19 in ATC. Expression of H19, miR-454-3p, and BHLHE40 mRNA was measured using RT-qPCR in tissue samples and cell lines. The dual-luciferase reporter assay and Pearson correlation analysis were used to explore the interaction among H19, miR-454-3p, and BHLHE40. The biological process of proliferation, migration, and invasion was determined using loss- or gain-function CCK-8 and Transwell assays. Western blot assay was used to evaluate the changes in protein levels. H19 was elevated in ATC tissues and cell lines. Based on online prediction database results, miR-454-3p might be a target of H19, and BHLHE40 might be a direct target of miR-454-3p. miR-454-3p expression was decreased in ATC and had a negative interaction with H19. BHLHE40 mRNA expression was increased and has a negative correlation with miR-454-3p and a positive correlation with H19. Downregulation of miR-454-3p and upregulation of BHLHE40 could reverse the decreased cellular activities caused by si-H19. Moreover, the silence of H19 modulates BHLHE40 to affect the PI3K/AKT protein levels and apoptotic-related protein levels. The current study provided a potential detailed mechanism of H19 in ATC, and lncRNA H19-miR-454-3p-BHLHE40 interaction may be a new experimental basis for prognosis and targeted therapy for ATC patients.
Insights
Long non-coding RNA H19 (H19) promotes anaplastic thyroid carcinoma (ATC) by downregulating miR-454-3p and upregulating BHLHE40. This H19-miR-454-3p-BHLHE40 axis offers a potential therapeutic target for ATC.
Area of Science:
- Molecular Oncology
- Cancer Biology
Background:
- Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy with limited therapeutic options.
- Previous research indicated that inhibiting long non-coding RNA H19 (lncRNA H19) suppresses ATC growth and metastasis.
Purpose of the Study:
- To elucidate the underlying molecular mechanism of H19 in the progression of ATC.
- To investigate the interaction between H19, miR-454-3p, and BHLHE40 in ATC.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) for gene expression analysis.
- Dual-luciferase reporter assay and Pearson correlation analysis to determine molecular interactions.
- Cellular assays (CCK-8, Transwell) and Western blot to assess functional impacts and protein levels.
Main Results:
- H19 expression was significantly elevated in ATC tissues and cell lines.
- H19 negatively regulated miR-454-3p, which was downregulated in ATC.
- BHLHE40 mRNA was upregulated in ATC, inversely correlated with miR-454-3p, and positively correlated with H19.
- H19 inhibition's effects on proliferation, migration, and invasion were reversed by miR-454-3p downregulation or BHLHE40 upregulation.
- H19 modulated BHLHE40 to impact PI3K/AKT and apoptosis-related protein levels.
Conclusions:
- The lncRNA H19-miR-454-3p-BHLHE40 axis plays a critical role in ATC pathogenesis.
- This molecular pathway represents a potential therapeutic target and prognostic marker for ATC patients.
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