Upregulation of microRNA-3129 suppresses epithelial ovarian cancer through CD44

Abstract

The purpose of this work is to evaluate whether human microRNA-3129 (hsa-miR-3129) may functionally regulate cancer development, possibly through downstream target CD44 in human epithelial ovarian cancer (EOC). Direct targeting of hsa-miR-3129 on human CD44 transcript was evaluated using a dual-luciferase reporter assay. Gene expression of hsa-miR-3129 in immortal EOC cell lines was evaluated by qRT-PCR. Lentivirus-mediated hsa-miR-3129 upregulation or downregulation was conducted in SK-OV-3 and CAOV-3 cells, in which endogenous hsa-miR-3129 and CD44 expressions were then measured. In hsa-miR-3129 upregulated or downregulated EOC cells, functional assays were applied to evaluate EOC proliferation, bufalin chemoresistance in vitro, or xenotransplantation in vivo. Moreover, CD44 was ectopically overexposed in hsa-miR-3129 upregulated EOC cells to functionally evaluate the correlation between hsa-miR-3129 and CD44 in EOC. Dual-luciferase reporter assay confirmed hsa-miR-3129 directly binds CD44. QRT-PCR revealed that hsa-miR-3129 was substantially downregulated in EOC cell lines. In SK-OV-3 and CAOV-3 cells, lentivirus-induced hsa-miR-3129 upregulation downregulated CD44 whereas hsa-miR-3129 downregulation did not affect CD44 expression. Hsa-miR-3129 upregulation had significant anti-cancer effects by inhibiting EOC proliferation, increasing bufalin chemoresistance, and suppressing xenotransplantation. On the other hand, overexpressing CD44 reversed the anti-cancer functions by hsa-miR-3129 upregulation in EOC cells. In conclusion, Has-miR-3129 is a functional regulator, possibly through reverse targeting on CD44, in EOC.

Retracted: Long noncoding RNA NORAD is upregulated in epithelial ovarian cancer and its downregulation suppressed cancer cell functions by competing with miR‐155‐5p

“…The method to evaluate EOC cancer cell proliferation in vitro was described in our previous study. 23 Briefly, OVCAR-3 and ES-2 cells were lifted off from 6-well plates and equally plated in a 96-well plate at a concentration of 5000 cells/well for 5 days. At each proliferating day, EOC cells were firstly treated with a CellTiter 96 ® Aqueous One Solution Cell Proliferation Assay (Promega, USA), and then examined on a spectraMax M3 multi-mode microplate reader (Molecular Devices, USA).…”

“…The method to assess EOC cancer cell in vitro chemoresistance was described in our previous study. 23 Briefly, OVCAR-3 and ES-2 cells were lifted off from 6-well plates and equally plated in a 96-well plate at a concentration of 5000 cells/well. Bufalin (Sigma Aldrich, USA) was added into tested wells at various concentrations of 0, 0.25, 1, 5, and 10 ng/mL for 48 hours.…”

HNRNPA2/B1 is upregulated in endocrine-resistant LCC9 breast cancer cells and alters the miRNA transcriptome when overexpressed in MCF-7 cells

“…Directly targets SIRT1 92 .oncomiR TAM-R Tumor suppressormiR-222-5p2.59Increased in TAM-R cells 54 ; Roles in BCa and TAM-R reviewed 7,34,39 ; high levels are associated with breast tumor stage 93 . Directly targets SSSCA1 (P27) 94 .oncomiR TAM-RmiR-302c-3p2.60Expression correlated with HER2+ in breast tumors 86 and development of breast cancer 95 ; Directly targets ESR1 (ERα) 96 , CCND1 (Cyclin D1) 97 ; BCRP 98 ; MEKK1 99 oncomiRmiR-3129-3p2.57Downregulated in epithelial ovarian cancer (EOC) cell lines and overexpression by lentiviral transduction inhibited EOC cell proliferation in vitro and tumor xenograft growth in vivo 100 .Tumor suppressor in EOCmiR-31322.13Upregulated in A549, HUVEC and THP-1 cells infected with a hantavirus (Prospect Hill virus) 101 miR-3135a2.60No references relevant to human cancer were foundmiR-31682.60Upregulated by 2 nM paclitaxel treatment in HepG2 cells and thought to play a role in paclitaxel resistance 102 .miR-31952.42Related to metastases 103 miR-36102.58Upregulated in BCa tissues 104 .miR-3619-3p2.20High expression in MCF-7 cells and acts as a tumor suppressor by directly targeting PLD (phospholipase D) 105 ; higher expression correlated with tumor relapse in small cell carcinoma of the esophagus 106 tumor suppressormiR-36553.26Upregulated in metastatic melanoma 107 .miR-36742.40No references relevant to cancer were foundmiR-39192.60No references relevant to cancer were foundmiR-39232.13Downregulated in primary breast tumors with lymph node metastasis 108 .tumor suppressormiR-39382.57No references relevant to cancer were foundmiR-3944-5p2.00Upregulated by hypoxia in AC16 cardiomyocytes 109 .miR-3960…”

Exosome mediated miR-155 delivery confers cisplatin chemoresistance in oral cancer cells via epithelial-mesenchymal transition

“…miR-760, for example was found to be downregulated in breast cancer cells, whilst its forced overexpression caused the sensitization towards doxorubicin via EMT reversal [42]. Likewise, miR-3129 upregulation mediated suppression of bufalin chemoresistance in epithelial ovarian cancer via CD44 regulation [43]. In contrast, upregulation of miR-30a, miR-375 and miR-376 in melanoma, cervical and ovarian cancer mediated resistance to chemotherapeutic drugs: cisplatin and paclitaxel [44][45][46].…”