RESUMEN
To study the clinical value of HEIH hyperexpression in gastric cancer and the molecular mechanism of promoting malignant proliferation of gastric cancer cells, qRT-PCR was used to detect the expression of HEIH in gastric cancer and nontumor gastric tissues. HEIH interference sequence was constructed to downregulate HEIH expression in MGC-803 and BGC-823 cell lines. CCK8, clonogenesis, and Transwell assay were used to detect the effects of HEIH on proliferation and invasion of tumor cells. The protein levels of STAT3, p-STAT3, P62, and LC3 were detected by Western blotting. The results showed that HEIH was highly expressed in gastric cancer (P < 0.01). Interference of HEIH expression in MGC-803 and BGC-823 cells reduced the proliferation and invasion of gastric cancer cells, and the results were statistically significant (P < 0.05). HEIH acts as a miRNA sponge for miR-4500. HEIH promotes gastric cancer development by inhibiting miR-4500. STAT3 is a downstream target of miR-4500. HEIH inhibits autophagy and promotes glycolysis. In conclusion, HEIH is highly expressed in gastric cancers. HEIH promotes malignant proliferation and development of gastric cancer cells. HEIH may be a new candidate site for pathological diagnosis and molecular drug therapy for future clinical treatment of gastric cancer.
Asunto(s)
MicroARNs , ARN Largo no Codificante , Neoplasias Gástricas , Autofagia , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Glucólisis , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Neoplasias Gástricas/patologíaRESUMEN
OBJECTIVE: Circular RNA (circRNA) plays a vital role in the development and progression of malignancies, however, the function of circRNAs in cholangiocarcinoma (CCA) remains unexplored. The aim of this study was to investigate circRNA expression in CCA versus para-cancer tissues, and elucidate any potential associated mechanisms. METHODS: Differential expression of circRNAs between CCA and para-cancer tissue was analysed by microarray hybridization, and validated by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The downstream pathway was investigated using bioinformatics and qRT-PCR. RESULTS: Microarray hybridization revealed 10 circRNAs with > 3-fold increased expression versus para-cancer (circRNA_002172, circRNA_002144, circRNA_001588, circRNA_000166, circRNA_000585, circRNA_000167, circRNA_402608, circRNA_006853, circRNA_001589, circRNA_008882), and three circRNAs with > 3-fold decreased expression (circRNA_406083, circRNA_104940, circRNA_006349). CircRNA_000585 was shown by qRT-PCR to be upregulated in tumour versus paired para-cancer tissue from 15 patients with CCA. Bioinformatics analysis revealed a potential pathway comprising circRNA_000585/microRNA-615-5p/angiomotin (AMOT)/Yes associated protein 1 (YAP) in CCA. RT-PCR validation of crucial molecule expression showed downregulation of miR-615-5p, and upregulation of AMOT and YAP in CCA tumours. CONCLUSION: Multiple circRNAs are dysregulated in CCA. CircRNA_000585 is upregulated in CCA, and may function by a circRNA_000585/miR-615-5p/AMOT/YAP pathway, which may be a novel CCA pathway.