| Autor: |
Phawinee Subsomwong, Hiroshi Ashida, Tokuju Okano, Lam Tung Nguyen, Mototsugu Tanaka, Ryota Otsubo, Hitomi Mimuro, Rui Yokomori, Takahito Sanada, Tuan Vo Phuoc, Kotaro Kiga, Tamako Iida, Yoshitoshi Ogura, Kenta Nakai, Yoshio Yamaoka, Dang Quy Dung Ho, Ryo Kinoshita-Daitoku, Eisuke Kuroda, Tran Thanh Binh, Arpana Sood, Toshihiko Suzuki, Tetsuya Hayashi, Zhu Bo, Sayaka Hirukawa, Khien Vu Van |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| DOI: |
10.1101/2020.02.15.950279 |
| Popis: |
Type-1 carcinogenic Helicobacter pylori that is known to evolve during long-term infection, enters the stomach orally and causes gastric cancer using the carcinogenic protein CagA1. However, little is known about the adaptation mechanisms of H. pylori when the environment changes from the outside to the inside of the living body. Here we show that small non-coding RNA HPnc4160 is a crucial novel RNA molecule of H. pylori that negatively regulates bacterial-host adaptation and gastric cancer. H. pylori isolated from gerbil’s stomachs eight weeks post-infection acquired mutations in the increased number of T-repeats within the upstream region of the HPnc4160 coding region, which leads to reduced HPnc4160 expression levels that also seen in cancer patients-derived H. pylori. By comparing RNA-seq and iTRAQ analysis between wild-type and hpnc4160 deficient mutant strains, we identified eight targets of HPnc4160 including cagA and unknown factors. Mice infection experiment revealed that the hpnc4160 deficient mutant had a higher number of colonized bacteria in the mice stomach than the wild-type strain, indicating that reduced expression levels of HPnc4160 was important for bacterial host adaptation. The expression level of HPnc4160 was lower in the clinical isolates derived from gastric cancer patients compared with non-cancer-derived strains, while the mRNA expression levels of target factors were higher. Our findings highlight the first discovery that HPnc4160 is an important small RNA for bacteria to adapt to the host environment leading to gastric carcinogenesis. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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