<p>The inhibitive effect of sh-HIF1A-AS2 on the proliferation, invasion, and pathological damage of breast cancer via targeting miR-548c-3p through regulating HIF-1&alpha;/VEGF pathway in vitro and vivo</p>

Abstract

BackgroundBreast cancer (BC) has been the commonest malignant tumor with a low survival rate among woman. Long non-coding RNA hypoxia-inducible factor-1 alpha antisense RNA-2 (HIF1A-AS2) was correlated with various cancers.PurposeThe study aimed to investigate the roles and related underlying molecular mechanisms of HIF1A-AS2 in BC.Material and methodsTarget relationships were speculated by Targetscan 7.0 and confirmed by dual luciferase reporter assay. Proteins levels were monitored by RT-qPCR, Western blot and immunohistochemistry assays. CCK-8 assay, SA-β-gal staining and transwell assay were used to detect proliferation, senescence and invasion, respectively. Xenograft nude mice were put into use to evaluate the tumor growth and motility.ResultsThe present study exhibited that HIF1A-AS2 and hypoxia-inducible factor-1 alpha (HIF-1α) were upregulated while miR-548c-3p was downregulated in MDA-MB-231, MCF-7, ZR-75-1, and BT-549 BC cell lines. Bioinformatics analysis showed HIF1A-AS2 and HIF-1α were two targets of miR-548c-3p, and the target relationship was further confirmed by dual luciferase reporter assay. Moreover, knockdown of HIF1A-AS2 by shRNA (sh-HIF1A-AS2) markedly elevated miR-548c-3p level, and the enhanced miR-548c-3p noticeably suppressed cell proliferation, invasion, and epithelial–mesenchymal transition, and promoted senescence in vitro. In addition, overexpression of HIF-1α promoted MCF-7 cell invasion. Intriguingly, low expression of HIF1A-AS2 reduced HIF-1α level by upregulating the expression of miR-548c-3p. Furthermore, experiment in xenograft nude mice has indicated that sh-HIF1A-AS2 inhibited tumor growth and motility by targeting miR-548c-3p through regulating HIF-1α/vascular endothelial growth factor (VEGF) pathway in vivo.ConclusionThe inhibitive effect of HIF-1α/VEGF pathway by sh-HIF1A-AS2 through targeting miR-548c-3p plays crucial regulatory roles in BC. Therefore, designing targeted drugs against HIF1A-AS2 provides a new direction for the treatment of BC.

<p>Long Noncoding RNA HIF1A-AS2 Promotes Non-Small Cell Lung Cancer Progression by the miR-153-5p/S100A14 Axis</p>

“…21 HIF1A-AS2 was also found to sponge several miRNAs, such as miR-129-5p, miR-548c-3p and miR-665. 12,22,23 In our study, we demonstrated that HIF1A-AS2 interacted with miR-153-5p. We showed that miR-153-5p expression was upregulated after HIF1A-AS2 knockdown, and HIF1A-AS2 level was negatively correlated with miR-153-5p expression in NSCLC tissues.…”

Natural antisense transcripts in the biological hallmarks of cancer: powerful regulators hidden in the dark

“…A few studies have discussed this hypothesis, such as in non-small cell lung cancer [ 135 ] and ovarian cancer [ 136 ], but it has not been validated experimentally. Despite that, HIF1A-AS2 can promote HIF1A expression and regulate the HIF1A/VEGFA pathway by sponging miR-548c-3p, exerting a proangiogenic function in breast cancer [ 137 ]. In bladder cancer samples following treatment with cisplatin (a chemotherapy drug), HIF1A-AS2 and HIF1A are both overexpressed and correlate positively [ 138 ].…”

Silencing of hsa_circ_0101145 reverses the epithelial-mesenchymal transition in hepatocellular carcinoma via regulation of the miR-548c-3p/LAMC2 axis

“…We also found that miR-548c-3p was a downstream target of hsa_circ_0101145. Previous studies have indicated that miR-548c-3p expression can inhibit the progression of many cancers, including papillary thyroid carcinoma [20], breast cancer [21], and osteosarcoma [22]. We found that miR-548c-3p expression decreased in HCC tissues.…”