Abstract
Background
Long noncoding RNAs (LncRNAs) have been reported to be abnormally
expressed in human ovarian cancer and associated with the proliferation and
metastasis of cancer cells. The objective of this study was to investigate the
role and the underlying mechanisms of LncRNA MAP3K20 antisense RNA 1 (MLK7-AS1)
in ovarian cancer.
Methods
The expression level of MLK7-AS1 was investigated in human ovarian
cancer tissues and cell lines. The effects of MLK7-AS1 knockdown on ovarian
cancer cell proliferation, migration, invasion and apoptosis were evaluated in
vitro using MTT, colony formation assays, wound healing assays, transwell assays
and flow cytometry. Furthermore, the in vivo effects were determined using the
immunodeficient NSG female mice. Luciferase reporter assays were employed to
identify interactions among MLK7-AS1 and its target genes.
Results
In the current study, MLK7-AS1 was specifically upregulated in
ovarian cancer tissues and cell lines. Knockdown of MLK7-AS1 inhibited the
ability of cell migration, invasion, proliferation, colony formation and wound
healing, whereas promoted cell apoptosis in vitro. By using online tools and
mechanistic analysis, we demonstrated that MLK7-AS1 could directly bind to
miR-375 and downregulate its expression. Besides, MLK7-AS1 reversed the
inhibitory effect of miR-375 on the growth of ovarian cancer cells, which might
be involved in the upregulation of Yes-associated protein 1 (YAP1) expression.
Moreover, knockdown MLK7-AS1 expression inhibited primary tumor growth in ovary
and metastatic tumors in multiple peritoneal organs including liver and spleen
in vivo, which were partly abolished by miR-375 inhibition. Mechanically, we
found that MLK7-AS1 modulated the epithelial-mesenchymal transition (EMT)
process by interacting with miR-375/YAP1 both in vivo and vitro, which promoted
the expression of Slug.
Conclusions
Taken together, our study showed for the first time that MLK7-AS1
interacted with miR-375 to promote proliferation, metastasis, and EMT process in
ovarian cancer cells through upregulating YAP1.
Antitumor properties of salinomycin on cisplatin-resistant human ovarian cancer cells in vitro and in vivo: Involvement of p38 MAPK activation
