Metabolic abnormalities are one of the main hallmarks of
cancer and are associated with chemoresistance. Therefore,
targeting the metabolic reprogramming of cancer cells has
the potential to overcome chemoresistance. Probiotic-derived
extracellular vesicles (EVs) play important roles in biological
function and intracellular communication. However, the inhibitory
effect of Lactobacillus plantarum-derived EVs (LpEVs)
on colorectal cancer (CRC) cells has not yet been elucidated.
This study clearly revealed that increased glycolysis in 5-fluorouracil
(5-FU)-resistant CRC cells (CRC/5FUR) is directly
related to chemoresistance and that the metabolic shift reversed
by LpEVs inhibits cancer cell proliferation and eventually
leads to apoptosis. Pyruvate dehydrogenase kinase 2
(PDK2), one of the crucial enzymes for enhancing glycolysis,
was upregulated in CRC/5FUR cells. In our study, LpEVs sensitized
CRC/5FUR cells to 5-FU by attenuating PDK2 expression
in p53-p21-dependent metabolic signaling, thereby
circumventing 5-FU resistance. We demonstrated the effect
of cellular responses to 5-FU by modifying the PDK2
expression level in both 5-FU-sensitive parental CRC and 5-
FU resistant CRC cell lines. Finally, we revealed that the PDK2
signaling pathway can potentially be targeted using LpEVs
treatment to overcome chemoresistant CRC, thereby providing
a potential strategy for CRC treatment by intervening in
tumor metabolism.
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Helicobacter pylori outer membrane inflammatory protein
A (OipA) was originally named for its role in inducing inflammation
in the host, as evidenced by high mucosal IL-8
levels. Expression of OipA is regulated by phase variation of
a CT dinucleotide-repeat located in the 5region of the gene.
However, little is known about OipA geographic diversity
across isolates. To address this gap, we conducted a large-scale
molecular epidemiologic analysis using H. pylori clinical isolates
obtained from two geographically distinct populations:
Korea and the United States (US). Most Korean isolates (98.7%)
possessed two copies of oipA located at two specific loci (A
and B) while all US isolates contained only one copy of oipA
at locus A. Furthermore, most Korean oipA (94.8%) possessed
three or less CT repeats while most US oipA (96.6%) contained
five or more CT repeats. Among the two copies, all Korean
H. pylori possessed at least one oipA ‘on’ phase variant while
the single copy of oipA in US isolates showed 56.2% ‘on’ and
43.8% ‘off.’ Thus, host differences seem to have driven geographic
diversification of H. pylori across these populations
such that OipA expression in US isolates is still regulated by
phase variation with 5 or more CT repeats, while Korean isolates
always express OipA; duplication of the oipA combined
with a reduction of CT repeats to three or less ensures continued
expression. En masse, these findings suggest that diversity
in the oipA gene copy number, CT repeats, and phase
variation among H. pylori from different populations may
confer a benefit in adaptation to particular host populations.
Citations
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Genetic diversity of the oipA gene among Helicobacter pylori isolates and clinical outcome in Vietnam Thi Hong Nhung Thai, Hong Phong Nguyen, Thi Hai Yen Nguyen, Thi Be Hai Nguyen, Thai Hoa Nguyen, Thi Mai Ngan Nguyen, Thi Minh Thi Ha Infection, Genetics and Evolution.2023; 112: 105438. CrossRef
Characterization of East-Asian Helicobacter pylori encoding Western EPIYA-ABC CagA Kavinda Tissera, Myeong-A Kim, Jing Lai, Sacheera Angulmaduwa, Aeryun Kim, D. Scott Merrell, Ji-Hye Kim, Hanfu Su, Jeong-Heon Cha Journal of Microbiology.2022; 60(2): 207. CrossRef