Increased expression of hypoxia-inducible factor-1 alpha and its impact on transcriptional changes and prognosis in malignant tumours of the ocular adnexa

Lange, Clemens; Lehnert, Patrick; Boneva, Stefaniya; Zhang, Peipei; Ludwig, Franziska; Boeker, Martin; Hoffmeier, Klaus; Horres, Ralf; Schlunck, Günther; Reinhard, Thomas; Böhringer, Daniel; Auw-Haedrich, Claudia

doi:10.1038/s41433-018-0172-6

Cited by 22 publications

(33 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…23 In PC, targeting HIF-1α and LOXL2 are widely believed as therapeutic strategies to prevention in tumorigenesis of this disease. 23 In PC, targeting HIF-1α and LOXL2 are widely believed as therapeutic strategies to prevention in tumorigenesis of this disease.…”

Section: Discussionmentioning

confidence: 99%

“…Hypoxia is a dominant regulator of HIF-1α and LOXL2 (HIF-1α directly transcriptional target) in the progression of various cancers. 23 In PC, targeting HIF-1α and LOXL2 are widely believed as therapeutic strategies to prevention in tumorigenesis of this disease. In hypoxia-injured cardiomyocyte, salidroside is an inducer of HIF-1α expression, and favors HIF-1α translocation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Salidroside ameliorated hypoxia‐induced tumorigenesis of BxPC‐3 cells via downregulating hypoxia‐inducible factor (HIF)‐1α and LOXL2

Chen

Kou

et al. 2019

J of Cellular Biochemistry

View full text Add to dashboard Cite

Herein, we found that salidroside suppressed hypoxia‐inducible factor 1 alpha (HIF‐1α) and lysyl oxidase‐like protein 2 (LOXL2) within human pancreatic cancer BxPC‐3 cells cultured both under normoxia and hypoxia condition. To investigate the effect of salidroside on tumorigenesis of BxPC‐3 cells and whether HIF‐1α and LXCL2 were involved in this process, cells transfected with or without LOXL2 overexpression vector, were treated with 50 μg/mL of salidroside or 50 μM of KC7F2 (a HIF‐1α inhibitor) under hypoxia. Cell viability and invasion were assessed using CCK‐8 and Transwell chamber assay, respectively. Expression of E‐cadherin and matrix metalloproteinase 2/9 (MMP 2/9) was determined, by Western blot analysis, to assess cell mobility at molecular levels. We confirmed that hypoxia increased LOXL2 and induced tumorigenesis of BxPC‐3 cells, as evidenced by promoted cell proliferation and invasion, enhanced MMP2/9 while reduced E‐cadherin. Interestingly, hypoxia‐induced carcinogenesis was significantly retarded by both salidroside and KC7F2, however, enhanced with LOXL2 overexpression. Besides, salidroside and KC7F2 reduced LOXL2, and reversed the tumorigenesis of BxPC‐3 cells induced by LOXL2 overexpression. Given the inhibitory effect of salidroside on HIF‐1α expression, our data suggested that: (1) LOXL2 was the mechanism, whereby salidroside and KC7F2 showed inhibitory effect on cancer progression of BxPC‐3 cells; (2) salidroside exerted its anticancer effect, most likely, by a HIF‐1α/LOXL2 pathway. In conclusion, salidroside was a novel therapeutic drug in pancreatic cancer, and downregulation of HIF‐1α and LXCL2 was the underlying mechanism.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Salidroside ameliorated hypoxia‐induced tumorigenesis of BxPC‐3 cells via downregulating hypoxia‐inducible factor (HIF)‐1α and LOXL2

Chen

Kou

et al. 2019

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…Fifteen 4‐µm‐thick FFPE conjunctival sections were collected and stored in tubes before RNA extraction. RNA isolation from FFPE specimens was carried out as previously described 12 . Briefly, total RNA was extracted from FFPE samples using the Quick‐RNA FFPE Kit (Zymo Research, Irvine, California).…”

Section: Methodsmentioning

confidence: 99%

“…RNA quality was determined via the RNA Pico Sensitivity Assay on a LabChip GXII Touch (PerkinElmer, Waltham, MA). RNA sequencing was performed using a massive analysis of complementary DNA ends (MACE), a 3′ RNA sequencing method, as previously described 12 . The barcoded libraries comprising unique molecule identifiers were sequenced on the NextSeq 500 (Illumina) with 1× 75 bp.…”

Section: Methodsmentioning

confidence: 99%

Expression of the COVID‐19 receptor ACE2 in the human conjunctiva

Lange

Wolf

Auw-Haedrich

et al. 2020

Journal of Medical Virology

Self Cite

121

107

View full text Add to dashboard Cite

SARS-CoV-2 is assumed to use angiotensin-converting enzyme 2 (ACE2) and other auxiliary proteins for cell entry. Recent studies have described conjunctival congestion in 0.8% of patients with laboratory-confirmed SARS-CoV-2, and there has been speculation that SARS-CoV-2 can be transmitted through the conjunctiva. However, it is currently unclear whether conjunctival epithelial cells express ACE2 and its cofactors. In this study, a total of 38 conjunctival samples from 38 patients, including 12 healthy conjunctiva, 12 melanoma, 7 squamous cell carcinoma and 7 papilloma samples, were analyzed using high-throughput RNA sequencing to assess mRNA expression of the SARS-CoV-2 receptor ACE2 and its cofactors including This article is protected by copyright. All rights reserved. Accepted ArticleTMPRSS2, ANPEP, DPP4, and ENPEP. ACE2 protein expression was assessed in eight healthy conjunctival samples using immunohistochemistry. Our results show that the SARS-CoV-2 receptor ACE2 is not substantially expressed in conjunctival samples on the mRNA (median 0.0 transcripts per million (TPM), min 0.0 TPM, max 1.7 TPM) and protein levels. Similar results were obtained for the transcription of other auxiliary molecules. In conclusion, this study finds no evidence for a significant expression of ACE2 and its auxiliary mediators for cell entry in conjunctival samples, making conjunctival infection with SARS-CoV-2 via these mediators unlikely.

show abstract

“…There are a number of publications already available on transcriptome analysis of fresh ocular tissue [3 -5]. In contrast, there are only few data on RNA sequencing from formalin-fixed paraffinembedded (FFPE) ocular tissue [6]. Whereas DNA acts as a long-term information repository in cells, mRNAs serve as a short-term information carrier for the production of proteins.…”

Section: Mrna a Mrna Bmentioning

confidence: 99%

RNA Sequencing of Formalin-Fixed and Paraffin-Embedded Tissue as a Complementary Method in Ophthalmopathology

Schlunck

Boneva

Wolf

et al. 2020

Klin Monbl Augenheilkd

Self Cite

View full text Add to dashboard Cite

The high-throughput method of “Next Generation Sequencing” (NGS) allows cost-effective decoding of the nucleotide sequences of millions of RNA molecules in a sample. This makes it possible to determine the number of distinct RNA molecules in tissues or cells and to use these data to draw conclusions. The entirety of RNAs, in particular mRNAs (messenger RNAs) as potential precursors of proteins, provides a comprehensive insight into the functional state of the cells and tissues under investigation. In addition to cell cultures or unfixed tissue, formalin-fixed and paraffin-embedded (FFPE) tissue can also be analysed for this purpose using specific methods. In this overview, the methodological strategy and its application to the field of ophthalmic histopathology are presented.

show abstract

Increased expression of hypoxia-inducible factor-1 alpha and its impact on transcriptional changes and prognosis in malignant tumours of the ocular adnexa

Abstract: HIF-1α protein is increased in malignant tumours of the ocular adnexa, which is associated with an increase in multiple HIF-1α-downstream factors and a trend towards an unfavourable clinical outcome.

Cited by 22 publications

References 33 publications

Salidroside ameliorated hypoxia‐induced tumorigenesis of BxPC‐3 cells via downregulating hypoxia‐inducible factor (HIF)‐1α and LOXL2

Salidroside ameliorated hypoxia‐induced tumorigenesis of BxPC‐3 cells via downregulating hypoxia‐inducible factor (HIF)‐1α and LOXL2

Expression of the COVID‐19 receptor ACE2 in the human conjunctiva

RNA Sequencing of Formalin-Fixed and Paraffin-Embedded Tissue as a Complementary Method in Ophthalmopathology

Contact Info

Product

Resources

About