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2017 ; 8
(45
): 78851-78869
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gab.com Text
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English Wikipedia
S-adenosylmethionine and methylthioadenosine inhibit cancer metastasis by
targeting microRNA 34a/b-methionine adenosyltransferase 2A/2B axis
#MMPMID29108270
Tomasi ML
; Cossu C
; Spissu Y
; Floris A
; Ryoo M
; Iglesias-Ara A
; Wang Q
; Pandol SJ
; Bhowmick NA
; Seki E
; Posadas EM
; Lu SC
Oncotarget
2017[Oct]; 8
(45
): 78851-78869
PMID29108270
show ga
MicroRNA-34a (miR-34a) is down-regulated in colorectal cancers (CRC) and required
for interleukin-6 (IL-6)-induced CRC metastasis. Mice lacking miR-34a developed
more invasive cancer in a colitis-associated cancer model. In the same model,
S-adenosylmethionine (SAMe) and methylthioadenosine (MTA) inhibited IL-6/STAT3
and lowered tumor burden. SAMe and MTA reduce the expression of methionine
adenosyltransferase 2A (MAT2A) and there are consensus binding sites for
miR-34a/b in the MAT2A 3'UTR. Here we examined whether SAMe/MTA influence
miR-34a/b expression and cancer metastasis. We found SAMe and MTA raised
miR-34a/b expression in CRC cell lines, inhibited migration and invasion in vitro
and liver metastasis in vivo. Like CRC, MAT2A and MAT2B expression is induced in
human pancreas and prostate cancers. Treatment with SAMe, MTA, miR-34a or miR-34b
inhibited MAT2A expression mainly at the protein level. MAT2B protein level also
fell because MAT2A and MAT2B enhance each other's protein stability.
Overexpressing miR-34a or miR-34b inhibited while MAT2A or MAT2B enhanced CRC
migration and invasion. Co-expressing either miR-34a/b had minimal to no effect
on MAT2A/MAT2B's ability to increase migration, invasion and growth. Taken
together, MAT2A and MAT2B are important targets of miR-34a/b and SAMe and MTA
target this axis, suppressing MAT2A/MAT2B while raising miR-34a/b expression,
inhibiting cancer metastasis.
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