let-7d-3p is associated with apoptosis and response to neoadjuvant chemotherapy in ovarian cancer

  • Authors:
    • Raúl García-Vázquez
    • Dolores Gallardo Rincón
    • Erika Ruiz-García
    • Abelardo Meneses García
    • Olga N. Hernández De La Cruz
    • Horacio Astudillo-De La Vega
    • David Isla-Ortiz
    • Laurence A. Marchat
    • Yarely M. Salinas-Vera
    • Ángeles Carlos-Reyes
    • Sullivan López-González
    • Rosalio Ramos-Payan
    • César López-Camarillo
  • View Affiliations

  • Published online on: April 12, 2018     https://doi.org/10.3892/or.2018.6366
  • Pages: 3086-3094
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Abstract

Altered expression of microRNAs contributes to the heterogeneous biological behavior of human malignancies and it may correlate with the clinical pathological features of patients. The let-7 microRNA family is frequently downregulated in human cancers and its aberrant expression may be a useful marker for prediction of the clinical response to therapy in patients. In the present study, we analyzed the expression of three members of the let-7 family (let-7a-3p, let-7d-3p and let-7f), which remains largely uncharacterized in ovarian cancer tissues. We also investigated the function of let-7d-3p in the apoptosis and sensitization to chemotherapy in ovarian cancer cells. Our data from stem-loop quantitative RT-PCR showed that expression of let-7a-3p and let-7d-3p, but not let-7f, was significantly (P<0.04) upregulated in ovarian tumors relative to that noted in normal ovarian tissues. Markedly, an increased expression of let‑7d-3p (also known as let-7d-3*) was associated with positive response to carboplatin/paclitaxel treatment in ovarian cancer patients. To investigate the biological relevance of let‑7d-3p, we knocked down its expression in SKOV-3 ovarian cancer cell line using antagomiRs. Loss of function analysis showed that inhibition of let-7d-3p significantly (P<0.05) impaired cell proliferation and activated apoptosis. In contrast, scratch/wound healing and Transwell chamber assays showed that migration and invasion abilities were not affected in the let-7d-3p-deficient SKOV-3 cancer cells. Notably, Annexin V assays showed a significant (P<0.05) increase in cell death of cancer cells treated with the let-7d-3p inhibitor plus carboplatin indicating a synergistic effect of the drug with antagomiR therapy. Gene ontology classification of predicted targets of let-7d-3p identified a number of genes involved in cellular pathways associated with therapy resistance such as ABC transporters, HIF-1, RAS and ErbB signaling. In summary, our findings showed that inhibition of let-7d-3 activates apoptosis and that its upregulation is associated with a positive response of ovarian cancer patients to carboplatin/paclitaxel chemotherapy.
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June-2018
Volume 39 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
García-Vázquez R, Gallardo Rincón D, Ruiz-García E, Meneses García A, Hernández De La Cruz ON, Astudillo-De La Vega H, Isla-Ortiz D, Marchat LA, Salinas-Vera YM, Carlos-Reyes Á, Carlos-Reyes Á, et al: let-7d-3p is associated with apoptosis and response to neoadjuvant chemotherapy in ovarian cancer. Oncol Rep 39: 3086-3094, 2018.
APA
García-Vázquez, R., Gallardo Rincón, D., Ruiz-García, E., Meneses García, A., Hernández De La Cruz, O.N., Astudillo-De La Vega, H. ... López-Camarillo, C. (2018). let-7d-3p is associated with apoptosis and response to neoadjuvant chemotherapy in ovarian cancer. Oncology Reports, 39, 3086-3094. https://doi.org/10.3892/or.2018.6366
MLA
García-Vázquez, R., Gallardo Rincón, D., Ruiz-García, E., Meneses García, A., Hernández De La Cruz, O. N., Astudillo-De La Vega, H., Isla-Ortiz, D., Marchat, L. A., Salinas-Vera, Y. M., Carlos-Reyes, Á., López-González, S., Ramos-Payan, R., López-Camarillo, C."let-7d-3p is associated with apoptosis and response to neoadjuvant chemotherapy in ovarian cancer". Oncology Reports 39.6 (2018): 3086-3094.
Chicago
García-Vázquez, R., Gallardo Rincón, D., Ruiz-García, E., Meneses García, A., Hernández De La Cruz, O. N., Astudillo-De La Vega, H., Isla-Ortiz, D., Marchat, L. A., Salinas-Vera, Y. M., Carlos-Reyes, Á., López-González, S., Ramos-Payan, R., López-Camarillo, C."let-7d-3p is associated with apoptosis and response to neoadjuvant chemotherapy in ovarian cancer". Oncology Reports 39, no. 6 (2018): 3086-3094. https://doi.org/10.3892/or.2018.6366