Abstract
Helicobacter pylori infection is a major risk factor for the development of gastric cancer. Aberrant expression of microRNAs is strongly implicated in gastric tumorigenesis; however, their contribution in response to H. pylori infection has not been fully elucidated. In this study, we evaluated the expression ofmiR-135b-5p and its role in gastric cancer. We describe the overexpression of miR-135b-5p in human gastric cancer tissue samples compared with normal tissue samples. Furthermore, we found that miR-135b-5p is also up-regulated in gastric tumors from the trefoil factor 1-knockout mouse model. Infection with H. pylori induced the expression of miR-135b-5p in the in vitro and in vivo models. miR-135b-5p induction was mediated by NF-kB. Treatment of gastric cancer cellswith TNF-a inducedmiR-135b-5p in aNF-kB-dependentmanner.Mechanistically,we found thatmiR-135b-5p targets Kr üppel-like factor 4 (KLF4) and binds to its 39 UTR, leading to reduced KLF4 expression. Functionally, high levels of miR-135b-5p suppress apoptosis and induce cisplatin resistance. Our results uncovered a mechanistic link between H. pylori infection andmiR-135b-5p-KLF4, suggesting that targetingmiR-135b-5p could be a potential therapeutic approach to circumvent resistance to cisplatin.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 264-274 |
| Number of pages | 11 |
| Journal | FASEB Journal |
| Volume | 33 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2019 |
Fingerprint
Keywords
- H. pylori
- Inflammation
- KLF4
- MicroRNA
- Tff1 knockout
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics
Cite this
Helicobacter pylori-induced miR-135b-5p promotes cisplatin resistance in gastric cancer. / Shao, Linlin; Chen, Zheng; Soutto, Mohammed; Zhu, Shoumin; Lu, Heng; Romero-Gallo, Judith; Peek, Richard; Zhang, Shutian; El-Rifai, Wael.
In: FASEB Journal, Vol. 33, No. 1, 01.01.2019, p. 264-274.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Helicobacter pylori-induced miR-135b-5p promotes cisplatin resistance in gastric cancer
AU - Shao, Linlin
AU - Chen, Zheng
AU - Soutto, Mohammed
AU - Zhu, Shoumin
AU - Lu, Heng
AU - Romero-Gallo, Judith
AU - Peek, Richard
AU - Zhang, Shutian
AU - El-Rifai, Wael
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Helicobacter pylori infection is a major risk factor for the development of gastric cancer. Aberrant expression of microRNAs is strongly implicated in gastric tumorigenesis; however, their contribution in response to H. pylori infection has not been fully elucidated. In this study, we evaluated the expression ofmiR-135b-5p and its role in gastric cancer. We describe the overexpression of miR-135b-5p in human gastric cancer tissue samples compared with normal tissue samples. Furthermore, we found that miR-135b-5p is also up-regulated in gastric tumors from the trefoil factor 1-knockout mouse model. Infection with H. pylori induced the expression of miR-135b-5p in the in vitro and in vivo models. miR-135b-5p induction was mediated by NF-kB. Treatment of gastric cancer cellswith TNF-a inducedmiR-135b-5p in aNF-kB-dependentmanner.Mechanistically,we found thatmiR-135b-5p targets Kr üppel-like factor 4 (KLF4) and binds to its 39 UTR, leading to reduced KLF4 expression. Functionally, high levels of miR-135b-5p suppress apoptosis and induce cisplatin resistance. Our results uncovered a mechanistic link between H. pylori infection andmiR-135b-5p-KLF4, suggesting that targetingmiR-135b-5p could be a potential therapeutic approach to circumvent resistance to cisplatin.
AB - Helicobacter pylori infection is a major risk factor for the development of gastric cancer. Aberrant expression of microRNAs is strongly implicated in gastric tumorigenesis; however, their contribution in response to H. pylori infection has not been fully elucidated. In this study, we evaluated the expression ofmiR-135b-5p and its role in gastric cancer. We describe the overexpression of miR-135b-5p in human gastric cancer tissue samples compared with normal tissue samples. Furthermore, we found that miR-135b-5p is also up-regulated in gastric tumors from the trefoil factor 1-knockout mouse model. Infection with H. pylori induced the expression of miR-135b-5p in the in vitro and in vivo models. miR-135b-5p induction was mediated by NF-kB. Treatment of gastric cancer cellswith TNF-a inducedmiR-135b-5p in aNF-kB-dependentmanner.Mechanistically,we found thatmiR-135b-5p targets Kr üppel-like factor 4 (KLF4) and binds to its 39 UTR, leading to reduced KLF4 expression. Functionally, high levels of miR-135b-5p suppress apoptosis and induce cisplatin resistance. Our results uncovered a mechanistic link between H. pylori infection andmiR-135b-5p-KLF4, suggesting that targetingmiR-135b-5p could be a potential therapeutic approach to circumvent resistance to cisplatin.
KW - H. pylori
KW - Inflammation
KW - KLF4
KW - MicroRNA
KW - Tff1 knockout
UR - http://www.scopus.com/inward/record.url?scp=85059226230&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059226230&partnerID=8YFLogxK
U2 - 10.1096/fj.201701456RR
DO - 10.1096/fj.201701456RR
M3 - Article
C2 - 29985646
AN - SCOPUS:85059226230
VL - 33
SP - 264
EP - 274
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 1
ER -