Life sciences · 2020
HOTAIRM1 suppresses cell proliferation and invasion in ovarian cancer through facilitating ARHGAP24 expression by sponging miR-106a-5p.
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Chao Hongtu, Zhang Mengli, Hou Hongyi, Zhang Zhenzhong, Li Nan
Аннотация
AIMS: Ovarian cancer (OC) is the most lethal gynecologic malignant tumors all over the world. HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) has been reported as an important regulator in multiple tumors. However, the functions of HOTAIRM1 in OC and its possible molecular mechanisms remain unclear.
MAIN METHODS: qRT-PCR analysis was performed to detect the expression levels of HOTAIRM1, miR-106a-5p and ARHGAP24 mRNA in OC tissues and cells. The functional effects of HOTAIRM1, miR-106a-5p and ARHGAP24 on OC cells were determined by MTT, colony formation, flow cytometry and Transwell assays. Luciferase reporter, RIP and RNA pull-down assays were used to examine the interaction between miR-106a-5p and HOTAIRM1 or ARHGAP24. Tumor xenografts were constructed in nude mice to confirm the roles of HOTAIRM1 in OC in vivo.
KEY FINDINGS: HOTAIRM1 expression was lowered in OC tumor tissues and cells. Decreased HOTAIRM1 expression was associated with advanced FIGO stages and lymphatic metastasis. Up-regulation of HOTAIRM1 suppressed OC cell proliferation and invasion, and promoted apoptosis. Also, HOTAIRM1 slowed OC tumor growth in vivo. Moreover, HOTAIRM1 could serve as a competing endogenous RNA (ceRNA) of miR-106a-5p to derepress ARHGAP24 expression. HOTAIRM1-mediated inhibitory effect on OC progression was partly reversed following the restoration of miR-106a-5p expression. Furthermore, ARHGAP24 overexpression repressed OC progression in vitro.
SIGNIFICANCE: In conclusion, our study showed that HOTAIRM1 suppressed OC progression through derepression of ARHGAP24 by sponging miR-106a-5p. This finding provides novel insights into the mechanisms of HOTAIRM1 in OC and highlights a potential therapeutic strategy for the treatment of OC.
MAIN METHODS: qRT-PCR analysis was performed to detect the expression levels of HOTAIRM1, miR-106a-5p and ARHGAP24 mRNA in OC tissues and cells. The functional effects of HOTAIRM1, miR-106a-5p and ARHGAP24 on OC cells were determined by MTT, colony formation, flow cytometry and Transwell assays. Luciferase reporter, RIP and RNA pull-down assays were used to examine the interaction between miR-106a-5p and HOTAIRM1 or ARHGAP24. Tumor xenografts were constructed in nude mice to confirm the roles of HOTAIRM1 in OC in vivo.
KEY FINDINGS: HOTAIRM1 expression was lowered in OC tumor tissues and cells. Decreased HOTAIRM1 expression was associated with advanced FIGO stages and lymphatic metastasis. Up-regulation of HOTAIRM1 suppressed OC cell proliferation and invasion, and promoted apoptosis. Also, HOTAIRM1 slowed OC tumor growth in vivo. Moreover, HOTAIRM1 could serve as a competing endogenous RNA (ceRNA) of miR-106a-5p to derepress ARHGAP24 expression. HOTAIRM1-mediated inhibitory effect on OC progression was partly reversed following the restoration of miR-106a-5p expression. Furthermore, ARHGAP24 overexpression repressed OC progression in vitro.
SIGNIFICANCE: In conclusion, our study showed that HOTAIRM1 suppressed OC progression through derepression of ARHGAP24 by sponging miR-106a-5p. This finding provides novel insights into the mechanisms of HOTAIRM1 in OC and highlights a potential therapeutic strategy for the treatment of OC.