scholarly journals MicroRNA-138 negatively regulates the hypoxia-inducible factor 1α to suppress melanoma growth and metastasis

2019 ◽  
Author(s):  
Haijiang Qiu ◽  
Fangchao Chen ◽  
Minjun Chen
Keyword(s):  
Hypoxia Inducible Factor ◽  
Significant Negative Correlation ◽  
Bioinformatic Analysis ◽  
Migration And Invasion ◽  
Rapid Progression ◽  
Hypoxia Inducible Factor 1Α ◽  
Melanoma Tissue ◽  
Melanoma Growth ◽  
A375 Cells

ABSTRACTMelanoma with rapid progression towards metastasis becomes the deadliest form of skin cancer. However, the mechanism of melanoma growth and metastasis is still unclear. Here, we found that miRNA-138 was low expression and hypoxia-inducible factor 1α (HIF1α) was high expression in the patient’s melanoma tissue, and they had a significant negative correlation (r = -0.937, P < 0.001). Patients with miRNA-138low/HIF1αhigh signature were predominant in late stage. Further, bioinformatic analysis demonstrated that miRNA-138 directly targeted HIF1α. We found that the introduction of miRNA-138 mimics to A375 cells could reduced HIF1α mRNA expression, and suppressed the cell proliferation, migration and invasion. Overexpression of miRNA-138 or inhibition of HIF1α significantly suppressed the growth and metastasis of melanoma in vivo. Our study demonstrates the role and clinical relevance of miRNA-138 and HIF1α in melanoma cell growth and metastasis, providing a novel therapeutic target for suppression of melanoma growth and metastasis.

scholarly journals Long Noncoding RNA MIR210HG is Induced by Hypoxia-inducible Factor 1α and Promotes Cervical Cancer Progression

2022 ◽  
Author(s):  
Xiao-lin Hu ◽  
Xia-tong Huang ◽  
Jia-ni Zhang ◽  
Jie Liu ◽  
Li-jun Wen ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Pulmonary Metastasis ◽  
Noncoding Rna ◽  
Hypoxia Inducible Factor ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Cervical Carcinogenesis ◽  
Hypoxia Inducible Factor 1Α

Abstract Background：Increasing evidence has indicated that long noncoding RNAs (lncRNAs) play essential roles in various types of cancer, especially the ability of tumor cells to adapt to hypoxia conditions. However, only a few of them have been experimentally validated in cervical squamous cell carcinoma (CSCC). Method: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to confirm the expression of MIR210HG in CSCC tissues compared with matched non-tumor tissues, and analyze its clinical significance. In vitro, RNA interference (siRNA) or overexpression plasmid was used to investigate the biological function and underlying mechanism of MIR210HG in cervical carcinogenesis. In vitro, cell proliferation and metastasis were evaluated by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. Furthermore, tumor growth and metastasis were evaluated in vivo using a xenogenous subcutaneously implant or a pulmonary metastasis model. Immunohistochemical staining or immunoblotting analysis was carried out to detect protein expression.Results：In the current study, we identified a hypoxia-induced lncRNA MIR210HG was excessively expressed in CSCC tissues and regulated by human papillomavirus (HPV) type 16 E6 and E7 via hypoxia-inducible factor 1α (HIF-1α). Functional assays revealed the role of MIR210HG in promoting proliferation, migration and invasion of CSCC cells in vitro under normoxia as well as hypoxia conditions. Meanwhile, stable MIR210HG silencing dramatically repressed tumor growth and pulmonary metastasis in vivo. Mechanistically, the depletion of MIR210HG or HIF-1α decreased each other’s expression level, while silencing MIR210HG or HIF-1α respectively downregulated the expression levels of phosphoglycerate kinase 1 (PGK1), one of key metabolic enzymes in the glycolysis pathway. Furthermore, decreased expression of PGK1 by HIF-1α knockdown was reversed through the overexpression of MIR210HG. Also, we demonstrated HIF-1α can activate the transcription of MIR210HG via binding its promoter. Conclusions: Taken together, these results expand our understanding of the cancer-associated functions of hypoxia-induced lncRNAs, and highlight MIR210HG forms a feedback loop with HIF-1α contributing to cervical carcinogenesis, with potential implications for therapeutic targeting.

Hypoxic Stress Upregulates the Expression of Slc38a1 in Brown Adipocytes via Hypoxia-Inducible Factor-1α

Pharmacology ◽  
2017 ◽  
Vol 101 (1-2) ◽  
pp. 64-71 ◽  
Author(s):  
Tetsuhiro Horie ◽  
Kazuya Fukasawa ◽  
Takashi Iezaki ◽  
Gyujin Park ◽  
Yuki Onishi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Hypoxia Inducible Factor ◽  
Amino Acid Transporters ◽  
Hypoxic Stress ◽  
Gene Encoding ◽  
Brown Adipocytes ◽  
Hypoxia Inducible Factor 1Α ◽  
Brown Adipose

The availability of amino acid in the brown adipose tissue (BAT) has been shown to be altered under various conditions; however, little is known about the possible expression and pivotal role of amino acid transporters in BAT under physiological and pathological conditions. The present study comprehensively investigated whether amino acid transporters are regulated by obesogenic conditions in BAT in vivo. Moreover, we investigated the mechanism underlying the regulation of the expression of amino acid transporters by various stressors in brown adipocytes in vitro. The expression of solute carrier family 38 member 1 (Slc38a1; gene encoding sodium-coupled neutral amino acid transporter 1) was preferentially upregulated in the BAT of both genetic and acquired obesity mice in vivo. Moreover, the expression of Slc38a1 was induced by hypoxic stress through hypoxia-inducible factor-1α, which is a master transcription factor of the adaptive response to hypoxic stress, in brown adipocytes in vitro. These results indicate that Slc38a1 is an obesity-associated gene in BAT and a hypoxia-responsive gene in brown adipocytes.

Chronic in vivo hypoxia in various organs: Hypoxia-inducible factor-1α and apoptosis

2006 ◽  
Vol 342 (3) ◽  
pp. 875-880 ◽  
Author(s):  
Paola Bianciardi ◽  
Monica Fantacci ◽  
Anna Caretti ◽  
Raffaella Ronchi ◽  
Giuseppina Milano ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1Α

scholarly journals In Vivo Topoisomerase I Inhibition Attenuates the Expression of Hypoxia-Inducible Factor 1α Target Genes and Decreases Tumor Angiogenesis

2011 ◽  
Vol 18 (1) ◽  
pp. 83-94 ◽  
Author(s):  
Eric Guérin ◽  
Wolfgang Raffelsberger ◽  
Erwan Pencreach ◽  
Armin Maier ◽  
Agnès Neuville ◽  
...  
Keyword(s):  
Tumor Angiogenesis ◽  
Topoisomerase I ◽  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1Α

Silencing of Hypoxia Inducible Factor-1α by RNA Interference Attenuates Human Glioma Cell Growth In vivo

2007 ◽  
Vol 13 (8) ◽  
pp. 2441-2448 ◽  
Author(s):  
David L. Gillespie ◽  
Kum Whang ◽  
Brian T. Ragel ◽  
Jeannette R. Flynn ◽  
David A. Kelly ◽  
...  
Keyword(s):  
Rna Interference ◽  
Cell Growth ◽  
Glioma Cell ◽  
Hypoxia Inducible Factor ◽  
Human Glioma ◽  
Human Glioma Cell ◽  
Hypoxia Inducible Factor 1Α

scholarly journals circLMTK2 acts as a sponge of miR-150-5p and promotes proliferation and metastasis in gastric cancer

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Sen Wang ◽  
Dong Tang ◽  
Wei Wang ◽  
Yining Yang ◽  
Xiaoqing Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Bioinformatic Analysis ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Normal Tissues ◽  
Tumour Metastasis ◽  
Genome Wide ◽  
Proliferation And Metastasis

Abstract Background As a novel class of non-coding RNAs, circular RNAs (circRNAs) are key regulators of the development and progression of different cancers. However, little is known about the function and biological mechanism of circLMTK2, also named hsa_circ_0001725, in gastric cancer (GC) tumourigenesis. Methods circLMTK2 was identified in ten paired cancer specimens and adjacent normal tissues by RNA sequencing and genome-wide bioinformatic analysis and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of circLMTK2 combined with in vitro and in vivo assays were performed to prove the functional significance of circLMTK2. The molecular mechanism of circLMTK2 was demonstrated by searching the CircNet database and confirmed by RNA in vivo precipitation assays, western blotting, luciferase assays and rescue experiments. Results circLMTK2 was frequently upregulated in GC tissues, and high circLMTK2 expression was associated with poor prognosis, lymph node metastasis and poor TNM stage in GC patients. Functionally, circLMTK2 overexpression promoted GC cell proliferation and tumourigenicity in vitro and in vivo. Furthermore, ectopic circLMTK2 expression enhanced GC cell migration and invasion in vitro and tumour metastasis in vivo. In addition, we demonstrated that circLMTK2 could sponge miR-150-5p, thus indirectly regulating the c-Myc expression and contributing to GC tumourigenesis. Conclusion Our findings demonstrate that circLMTK2 functions as a tumour promoter in GC through the miR-150-5p/c-Myc axis and could thus be a prognostic predictor and therapeutic target for GC.

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