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HMGA1 exacerbates tumor growth through regulating the cell cycle and accelerates
migration/invasion via targeting miR-221/222 in cervical cancer
#MMPMID29789601
Fu F
; Wang T
; Wu Z
; Feng Y
; Wang W
; Zhou S
; Ma X
; Wang S
Cell Death Dis
2018[May]; 9
(6
): 594
PMID29789601
show ga
High-mobility group AT-hook1 (HMGA1, formerly HMG-I/Y), an architectural
transcription factor, participates in a number of tumor biological processes.
However, its effect on cervical cancer remains largely indistinct. In this study,
we found that HMGA1 was generally overexpressed in cervical cancer tissues and
was positively correlated with lymph node metastasis and advanced clinical stage.
Via exogenously increasing or decreasing the expression of HMGA1, we showed that
HMGA1 affected the proliferation, colony formation, migration and invasion of
cervical cancer cells in vitro. Rescue experiments suggested that miR-221/222
could partly reverse HMGA1-mediated migration and invasion processes.
Mechanistically, we discovered that HMGA1 accelerated the G1/S phase transition
by regulating the expression of cyclin D1 and cyclin E1, which was consistent
with the results of the in vivo experiment. Furthermore, we found that HMGA1
regulated the expression of the miR-221/222 cluster at the transcriptional level
and that miR-221/222 targeted the 3'UTR of tissue inhibitor of metalloproteinases
3(TIMP3). We propose a fresh perspective that HMGA1 participates in the migration
and invasion process via the miR-221/222-TIMP3-MMP2/MMP9 axis in cervical cancer.
In summary, our study identified a critical role played by HMGA1 in the
progression of cervical cancer and the potential mechanisms by which exerts its
effects, suggesting that targeting HMGA1-related pathways could be conducive to
the therapies for cervical cancer.
|Base Sequence
[MESH]
|Cell Cycle/*genetics
[MESH]
|Cell Line, Tumor
[MESH]
|Cell Movement/*genetics
[MESH]
|Cell Proliferation/genetics
[MESH]
|Clone Cells
[MESH]
|Cyclin D1/metabolism
[MESH]
|Cyclin E/metabolism
[MESH]
|Epithelium/metabolism/pathology
[MESH]
|Female
[MESH]
|G1 Phase/genetics
[MESH]
|Gene Expression Regulation, Neoplastic
[MESH]
|HMGA1a Protein/*metabolism
[MESH]
|Humans
[MESH]
|Matrix Metalloproteinases/metabolism
[MESH]
|MicroRNAs/genetics/*metabolism
[MESH]
|Middle Aged
[MESH]
|Models, Biological
[MESH]
|Neoplasm Invasiveness
[MESH]
|S Phase/genetics
[MESH]
|Tissue Inhibitor of Metalloproteinase-3/metabolism
[MESH]
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