Dexmedetomidine mediates microRNA-185 to suppress ovarian cancer growth via inhibiting the SOX9/Wnt/β-catenin signaling pathway
2020
Objective: Cervical cancer (CC) is a serious health problem, causing heavy burden each year worldwide. Long non-coding RNA (lncRNA) is implicated in CC progression. This study aims to clarify the underlying mechanism of lncRNA HAND2 AS1 in CC cellular process.
Method: LncRNA expression in CC tissues and adjacent tissues was analyzed via Gene Expression Omnibus microarray. The levels of HAND2-AS1, microRNA (miR)-21 and ALEX1 in 54 cases of CC tissues, adjacent tissues, CC cell lines and normal breast cells were detected. The malignant biological behaviors of CC cells were detected after overexpressing HAND2-A S1 or inhibiting miR-21 expression. Bioinformatics analysis, luciferase reporter assay and RNA-pull down assay were performed to verify the relationship among HAND2-AS1, miR-21 and ALEX1. The effects of HAND2-AS1 on CC cell growth in vivo were verified by nude mice transplantation experiment.
Results: HAND2-AS1 was lowly expressed in CC tissues and cells, and HAND2-AS1 functioned as a competitive endogenous RNA of miR-21 and enhanced ALEX1 expression and downregulated JAK1/STAT3 pathway to inhibit malignant biological behavior of CC cells. Overexpression of HAND2-AS1 or silencing of miR-21 can inhibit the malignant biological behavior of CC cells. Moreover, overexpression of HAND2-AS1 can inhibit the growth of CC cells in vivo.
Conclusion: Our data supported that lncRNA HAND2-AS1 promoted ALEX1 expression through competitively binding to miR-21, thereby inhibiting the proliferation and epithelial-mesenchymal transformation and promoting apoptosis of CC cells.
Keyword: Cervical cancer; LncRNA HAND2-AS1; microRNA-21; Competitive endogenous RNA; ALEX1; JAK1/STAT3 pathway
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