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  • 1 Department of Physiology, Jining Medical University, Jining, Shandong, China
  • | 2 School of International Education, Xinxiang Medical University, Xinxiang, Henan, China
  • | 3 Department of Urology Surgery, The First People's Hospital of Shangqiu, Shangqiu, Henan, China
  • | 4 Department of Physiology, Zhengzhou University, Zhengzhou, Henan, China
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Abstract

Background

Hypoxia is a pivotal initiator of tumor angiogenesis and growth through the stabilization of hypoxia-inducible factors (HIFs). This study set out to examine the involvement of HIF-1α and HIF-2α in colon cancer and ascertained whether ORAI3 was involved in the pathway.

Materials and methods

Patients and murine models as well as human colorectal adenocarcinoma tumor (CW2) cells were included to examine the levels of ORAI1/3 and HIF-1/2α levels. Calcium imaging was utilized to ascertain the activity of calcium channel. Scratch assay was used to assess the migration capacity of the cells.

Results

Tumors from murine colon cancer xenograft models and patients with colon cancer displayed high ORAI1/3 and HIF-1/2α levels. Hypoxia treatment, mimicking the tumor microenvironment in vitro, increased ORAI1/3 and HIF-1/2α expression as well as store-operated Ca2+ entry (SOCE). Of note is that HIF-1/2α silencing decreased SOCE, and HIF-1/2α overexpression facilitated SOCE. Furthermore, ORAI3 rather than ORAI1 expression was inhibited by HIF-1/2α silencing while increased by ML228. Luciferase assay also confirmed that ORAI3 was elevated in the presence of ML228, indicating the linkage between HIF-1/2α and ORAI3. Additionally, colony-forming potential and cell migration capacity were decreased in siHIF-1α and siHIF-2α as well as siORAI3 cells, and the facilitating effect of ML228 on cell migration and colony-forming potential was also decreased in siORAI3 CW-2 cells, which points out the importance of ORAI3 in HIF1/2α pathway.

Conclusion

Our findings allow to conclude that both HIF-1α and HIF-2α facilitate ORAI3 expression, hence enhancing colon cancer progression.

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2020  
Total Cites 245
WoS
Journal
Impact Factor
2,090
Rank by Physiology 62/81 (Q4)
Impact Factor  
Impact Factor 1,866
without
Journal Self Cites
5 Year 1,703
Impact Factor
Journal  0,51
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Rank by Journal  Physiology 67/84 (Q4)
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Citable 42
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Articles
Total 0
Reviews
Scimago 29
H-index
Scimago 0,417
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Scimago Physiology (medical) Q3
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Scopus 270/1140=1,9
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Scopus Physiology (medical) 71/98 (Q3)
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Scopus 0,528
SNIP  
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2019  
Total Cites
WoS
137
Impact Factor 1,410
Impact Factor
without
Journal Self Cites
1,361
5 Year
Impact Factor
1,221
Immediacy
Index
0,294
Citable
Items
34
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Articles
33
Total
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Cited
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Citing
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Scimago
H-index
27
Scimago
Journal Rank
0,267
Scopus
Scite Score
235/157=1,5
Scopus
Scite Score Rank
Physiology (medical) 73/99 (Q3)
Scopus
SNIP
0,38

 

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Physiology International
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