Cancers, Vol. 13, Pages 4617: Let-7i Reduces Aggressive Phenotype and Induces BRCAness in Ovarian Cancer Cells

Cancers, Vol. 13, Pages 4617: Let-7i Reduces Aggressive Phenotype and Induces BRCAness in Ovarian Cancer Cells Cancers doi: 10.3390/cancers13184617 Authors: Evgeny Chirshev Tise Suzuki Hanmin Wang Anthony Nguyen Nozomi Hojo Linda Sanderman Saied Mirshahidi Yevgeniya J. Ioffe Juli J. Unternaehrer 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 BRCAness 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 BRCAness 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 ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research