Overexpression of HPV16 E6/E7 mediated HIF-1α upregulation of GLUT1 expression in lung cancer cells

Fan, Rong; Hou, Wei; Zhao, Yujie; Liu, Shuli; Qiu, Xueshan; Wang, Enhua; Wu, Guang-Ping

doi:10.1007/s13277-015-4221-5

Cited by 58 publications

(70 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GLUT1 is a glucose transporter that as the glucose influx into a cell is the first rate-limiting process involved in glucose metabolism. 16,17 HKII is a key enzyme that catalyzes the first step in the glycolysis pathway. 18,19 These two enzymes are key enzymes in the regulation of cellular glycolysis and energy metabolism.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-124 suppresses proliferation and glycolysis in non–small cell lung cancer cells by targeting AKT–GLUT1/HKII

Zhao

Chu

et al. 2017

Tumour Biol.

View full text Add to dashboard Cite

Non-small cell lung cancer accounts for 85% of all types of lung cancer and is the leading cause of worldwide cancerassociated mortalities. MiR-124 is epigenetically silenced in various types of cancer and plays important roles in tumor development and progression. MiR-124 was also significantly downregulated in non-small cell lung cancer patients. Glycolysis has been considered as a feature of cancer cells; hypoxia-inducible factor 1-alpha/beta and Akt are key enzymes in the regulation of glycolysis and energy metabolism in cancer cells. However, the role of miR-124 in non-small cell lung cancer cell proliferation, glycolysis, and energy metabolism remains unknown. In this research, cell proliferation was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; furthermore, glucose consumption and lactic acid production were assessed; adenosine triphosphate content and NAD + /NADH were also detected. These tests were conducted using the normal non-small cell lung cancer cell line A549, which was transfected variedly with miR-mimics, miR-124 mimics, miR-124 inhibitor, pc-DNA3.1(+)-AKT1, and pc-DNA3.1(+)-AKT2 plasmid. Here, we show that miR-124 overexpression directly decreased cell growth, glucose consumption, lactate production, and energy metabolism. MiR-124 also negatively regulates glycolysis rate-limiting enzymes, glucose transporter 1 and hexokinase II. Our results also showed that miR-124 negatively regulates AKT1 and AKT2 but no regulatory effect on hypoxiainducible factor 1-alpha/beta. Overexpression of AKT reverses the inhibitory effect of miR-124 on cell proliferation and glycolytic metabolism in non-small cell lung cancer. AKT inhibition blocks miR-124 silencing-induced AKT1/2, glucose transporter 1, hexokinase II activation, cell proliferation, and glycolytic or energy metabolism changes. In summary, this study demonstrated that miR-124 is able to inhibit proliferation, glycolysis, and energy metabolism, potentially by targeting AKT1/2-glucose transporter 1/hexokinase II in non-small cell lung cancer cells.

show abstract

Section: Discussionmentioning

confidence: 99%

MicroRNA-124 suppresses proliferation and glycolysis in non–small cell lung cancer cells by targeting AKT–GLUT1/HKII

Zhao

Chu

et al. 2017

Tumour Biol.

View full text Add to dashboard Cite

show abstract

“…A previous study investigated the association between glucose transporter 1 (GLUT1) and various tumor types, and identified that the abnormal expression of GLUT1 and other relevant genes may be associated with the intensive glucose metabolism in malignant cells (18). Previous studies have demonstrated that the transcription of GLUT1 is enhanced by HIF-1α in other solid types of cancer under hypoxic conditions (19,20), and glycolysis is enhanced to compensate for the increased energy demands (21,22). Therefore, HIF-1α and GLUT1 may also be associated with the regulation of certain oncogenes and growth factors in GC.…”

Section: Introductionmentioning

confidence: 99%

Correlation and expression analysis of hypoxia‑inducible factor�1α, glucose transporter 1 and lactate dehydrogenase�5 in human gastric cancer

Liu

Tian

et al. 2019

Oncol Lett

View full text Add to dashboard Cite

The development and identification of novel potential targeting sites for intervention therapy are essential in the search for improved treatment methods for gastric cancer (GC). Previously, it has been reported that hypoxia inducible factor-1α (HIF-1α) is a potential target gene involved in the endogenous hypoxic response and bioenergetic metabolism of GC cells. In the present study, with the assumption of a close interplay among HIF-1α, glucose transporter 1 (GLUT1) and lactate dehydrogenase-5 (LDH-5), 85 patients with GC were recruited and the protein and gene expression levels of HIF-1α, GLUT1 and LDH-5 in tumor tissues were evaluated in order to assess clinical correlations and co-expression patterns, using Immunohistochemical staining and reverse transcription-quantitative polymerase chain reaction. The results demonstrated that the protein and gene expression levels of HIF-1α were significantly associated with the depth of invasion, nodal metastasis, clinical stage, differentiation and distant metastasis. Consistent with the protein expression results, the mRNA expression levels of the genes coding for GLUT1 and LDH-5 were clearly associated with tumor size, depth of invasion, distant metastasis, clinical stage and differentiation. Correlation analysis of HIF-1α with GLUT1 and LDH-5 at the protein and mRNA expression levels in gastric carcinoma indicated that HIF-1α expression was positively correlated with the expression of GLUT1 (P<0.01, r=0.765 for mRNA expression; P<0.01, r= 0.697 for protein expression) and LDH-5 (P<0.01, r= 0.892 for mRNA expression; P<0.01, r= 0.783 for protein expression) at the mRNA and protein levels. Therefore, it may be concluded that HIF-1α, GLUT1 and LDH-5 are potential target genes involved in the endogenous tumor response to hypoxia and the inhibition of tumor energy metabolism, highlighting a novel therapeutic target for GC.

show abstract

“…The screening of lung cancer cell lines Based on our previous results, H1299 cell line was low E6 and E7 expression cell line, and A549 cell line was high E6 and E7 expression cell line [21]. The expression of KIF7 was screened in normal bronchial epithelial cell line HBE and lung cancer lines H1299, H460, and A549, respectively.…”

Section: Resultsmentioning

confidence: 99%

HPV16-E6 but not E7 inhibits the antitumor activity of LKB1 in lung cancer cells by down regulating the expression of KIF7

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background: The E6 and E7 proteins in HPV16 are the main oncogenes in the occurrence of lung cancer. In recent studies, we had found that E6 and E7 downregulated the expression of LKB1 in lung cancer cells. However, it is not clear how E6 and E7 regulate LKB1 in lung cancer cells. Methods: The double directional genetic manipulation and Nuclear plasma separation technology were performed to explore the molecular mechanism of E6 and E7 inhibiting the antitumor activity of LKB1 in well-established lung cancer cell lines. Results: E6 but not E7 significantly downregulated the expression of tumor suppressor KIF7 at protein level, and the inhibition of KIF7 further reduced the expression of LKB1 both in the nuclei and in the cytoplasm, whereas reduced the expression of p-LKB1 in the cytoplasm only. Therefore, we suggested that HPV16 E6 but not E7 downregulates the antitumor activity of LKB1 by down regulating the expression of p-LKB1 in the cytoplasm only. Conclusion: We demonstrated for the first time that E6 but not E7 inhibits the antitumor activity of LKB1 in lung cancer cells by downregulating the expression of KIF7. Our findings provided new evidence to support the important role of KIF7 in the pathogenesis of lung cancer and suggested new therapeutic targets.

show abstract

Overexpression of HPV16 E6/E7 mediated HIF-1α upregulation of GLUT1 expression in lung cancer cells

Cited by 58 publications

References 39 publications

MicroRNA-124 suppresses proliferation and glycolysis in non–small cell lung cancer cells by targeting AKT–GLUT1/HKII

MicroRNA-124 suppresses proliferation and glycolysis in non–small cell lung cancer cells by targeting AKT–GLUT1/HKII

Correlation and expression analysis of hypoxia‑inducible factor�1α, glucose transporter 1 and lactate dehydrogenase�5 in human gastric cancer

HPV16-E6 but not E7 inhibits the antitumor activity of LKB1 in lung cancer cells by down regulating the expression of KIF7

Contact Info

Product

Resources

About