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Indirect regulation of TFPI-2 expression by miR-494 in breast cancer cells.

ABSTRACT: TFPI-2 has been shown to be involved in breast cancer pathogenesis by inhibiting extracellular matrix degradation, and low levels are associated with disease progression. As microRNA-494 (miR-494) protects against breast cancer progression, we investigated whether miR-494 is involved in the regulation of TFPI-2 in MCF-7 breast cancer cells. TFPI-2 mRNA and protein levels increased after transfection with miR-494 mimic, and TFPI-2 mRNA and miR-494 levels correlated positively in tumors from breast cancer patients. No specific binding sites for miR-494 in the 3'-untranslated region (UTR) of TFPI2 were identified; however, miR-494 was predicted in silico to bind 3'-UTR of the transcription factors AHR and ELF-1, which have potential binding sites in the TFPI2 promoter. ELF-1 mRNA was downregulated whereas AHR mRNA levels were upregulated after transfection with miR-494 mimic. Knockdown of ELF-1 and AHR increased and reduced TFPI-2 mRNA levels, respectively. Increased luciferase activity was seen when TFPI-2 promoter constructs containing the potential AHR or ELF-1 binding sites were co-transfected with miR-494 mimic. In conclusion, TFPI-2 mRNA levels were upregulated by miR-494 in MCF-7 breast cancer cells most likely by an indirect association where miR-494 targeted the transcription factors AHR and ELF-1. This association was supported in a breast cancer cohort.

SUBMITTER: Andresen MS

PROVIDER: S-EPMC7055239 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Indirect regulation of TFPI-2 expression by miR-494 in breast cancer cells.

Andresen Marianne S MS Stavik Benedicte B Sletten Marit M Tinholt Mari M Sandset Per Morten PM Iversen Nina N Skretting Grethe G

Scientific reports 20200304 1

TFPI-2 has been shown to be involved in breast cancer pathogenesis by inhibiting extracellular matrix degradation, and low levels are associated with disease progression. As microRNA-494 (miR-494) protects against breast cancer progression, we investigated whether miR-494 is involved in the regulation of TFPI-2 in MCF-7 breast cancer cells. TFPI-2 mRNA and protein levels increased after transfection with miR-494 mimic, and TFPI-2 mRNA and miR-494 levels correlated positively in tumors from breas ...[more]

PMID: 32132611

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Project description:It is unclear how microRNA (miR)-494 inhibits the proliferation of cervical cancer cells by altering the expression of SOCS6. Therefore, the present study aimed to investigate the molecular mechanism underlying miR-494 regulation of suppressor of cytokine signaling 6 (SOCS6) in human cervical cancer samples and the human cervical cancer HeLa cell line. The expression of miR-494 was determined using reverse transcription-quantitative polymerase chain reaction. In addition, TargetScan was used to predict miR-494 target genes and the luciferase reporter assay was used to determine whether SOCS6 was a direct target of miR-494. The results of the present study demonstrated that compared with the cervical intraepithelial neoplasia and normal cervical tissues, the miR-494 expression level in cervical cancer samples was significantly decreased (P<0.01). In addition, compared with normal cervical tissue, miR-494 expression level was significantly decreased in cervical intraepithelial lesions (P<0.05). Furthermore, the expression of miR-494 was associated with patients with or without lymph node metastasis, clinical stage and depth of stromal invasion (P<0.01); however, miR-494 expression was not identified to be associated with age, tumor size and menopausal status (P>0.05). Transfection of a miR-494 mimic significantly increased the expression level of miR-494 in HeLa cells (P<0.01), and anti-miR-494 transfection decreased the expression of miR-494 (P<0.01). An MTT proliferation assay and Boyden chamber invasion ability assay revealed that miR-494 mimic transfection significantly inhibited the proliferation, and invasion ability of HeLa cells (P<0.01), whereas anti-miR-494 transfection significantly increased the proliferation and invasion ability (P<0.05). SOCS6 was predicted, using bioinformatics, to be the target gene of miR-494 and this was validated using a luciferase reporter assay. Western blot analysis revealed that transfection of miR-494 significantly increased the expression of SOCS6 in HeLa cells, and transfection of anti-miR-494 significantly decreased the expression of SOCS6. Therefore, the results of the present study demonstrated that miR-494 expression in cervical cancer was significantly decreased. Exhibiting a decreased expression level of miR-494 may result in enhanced proliferative and invasive abilities of HeLa cell, thus contributing to the occurrence, and development of cervical cancer.

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Indirect regulation of TFPI-2 expression by miR-494 in breast cancer cells.

Publications

Indirect regulation of TFPI-2 expression by miR-494 in breast cancer cells.

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