| Autor: |
Chirshev E; Department of Basic Sciences, Division of Biochemistry, Loma Linda University, Loma Linda, CA 92354, USA.; Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA., Suzuki T; Department of Basic Sciences, Division of Biochemistry, Loma Linda University, Loma Linda, CA 92354, USA., Wang H; Department of Basic Sciences, Division of Biochemistry, Loma Linda University, Loma Linda, CA 92354, USA., Nguyen A; Department of Basic Sciences, Division of Biochemistry, Loma Linda University, Loma Linda, CA 92354, USA., Hojo N; Department of Basic Sciences, Division of Biochemistry, Loma Linda University, Loma Linda, CA 92354, USA., Sanderman L; Department of Basic Sciences, Division of Biochemistry, Loma Linda University, Loma Linda, CA 92354, USA.; Biology Department, California State University San Bernardino, San Bernardino, CA 92407, USA., Mirshahidi S; Biospecimen Laboratory, Loma Linda University Cancer Center, Department of Basic Sciences, Division of Microbiology & Molecular Genetics, Loma Linda University, Loma Linda, CA 92354, USA., Ioffe YJ; Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, Loma Linda University Medical Center, Loma Linda, CA 92354, USA., Unternaehrer JJ; Department of Basic Sciences, Division of Biochemistry, Loma Linda University, Loma Linda, CA 92354, USA.; Department of Gynecology and Obstetrics, Loma Linda University, Loma Linda, CA 92354, USA.; Center for Health Disparities and Molecular Medicine, Loma Linda University, Loma Linda, CA 92354, USA. |
| Abstrakt: |
High-grade serous carcinoma of the ovary is a deadly gynecological cancer with poor long-term survival. Dysregulation of microRNAs has been shown to contribute to the formation of cancer stem cells (CSCs), an important part of oncogenesis and tumor progression. The let-7 family of microRNAs has previously been shown to regulate stemness and has tumor suppressive actions in a variety of cancers, including ovarian. Here, we demonstrate tumor suppressor actions of let-7i: repression of cancer cell stemness, inhibition of migration and invasion, and promotion of apoptosis, features important for cancer progression, relapse, and metastasis. Let-7i over-expression results in increased sensitivity to the PARP inhibitor olaparib in samples without BRCA mutations, consistent with induction of BRCA ness phenotype. We also show that let-7i inhibits the expression of several factors involved in the homologous recombination repair (HRR) pathway, providing potential mechanisms by which the BRCA ness phenotype could be induced. These actions of let-7i add to the rationale for use of this miRNA as a treatment for ovarian cancer patients, including those without mutations in the HRR pathway. |
