We identified several miRNAs in serum that distinguished subjects with endometriosis from those without. miR-125b-5p had the greatest potential as a single diagnostic biomarker. A combination of that miRNA with miR-451a and miR-3613-5p further improved diagnostic performance.
Higher Lin28 expression is associated with worse pathologic tumor responses in locally advanced gastric cancer patients undergoing neoadjuvant chemotherapy. However, the characteristics of Lin28 and its mechanism of action in chemotherapy resistance is still unclear. In this study, we found that transfection of Lin28 into gastric cancer cells (MKN45 and MKN28) increased their resistance to the chemo-drugs oxaliplatin (OXA), paclitaxel (PTX), doxorubicin (ADM), and fluorouracil (5-Fu) compared with gastric cancer cells transfected with a control vector. When knockdown Lin28 expression by Lin28 small interfering RNA (siRNA) was evaluated in vitro, we found that the resistance to chemo-drugs was reduced. Furthermore, we found that Lin28 up-regulates C-myc and P-gp and down-regulates Cylin D1. Finally, we found that miR-107 is a target microRNA of Lin28 and that it participates in the mechanism of chemotherapy resistance. Our results suggest that the Lin28/miR-107 pathway could be one of many signaling pathways regulated by Lin28 and associated with gastric cancer chemo-resistance.
Endometriosis is a chronic disease that commonly affects women of reproductive age; however, diagnosis is often delayed due to lack of appreciation of early signs and symptoms. Development of a noninvasive biomarker would significantly reduce delays in diagnosis and treatment. Circulating microRNAs (miRNAs) have been implicated as biomarkers for several diseases including endometriosis. Here, we use an miRNA array to investigate differential miRNA abundance in the serum of mice after induction of experimental endometriosis. let-7a-5p was decreased in the serum of mice with endometriosis. let-7b-5p, c-5p, and e-5p also showed a trend toward downregulation. Serum let-7 family miRNA shows similar dysregulation in endometriosis in both humans and mice. Diminished circulating let-7 implies a complex regulation that potentially involves multiple organs. Further investigation is necessary to determine the functional roles of let-7 miRNAs in this disease.
The RNA binding protein Lin28 is best known for the critical role in cell development, recent researches also have implied its oncogenic function in various human cancers, including breast cancer. Specifically, aberrant Lin28 participates in multiple pathological processes, such as proliferation, metastasis, radiotherapy and chemotherapy resistance, metabolism, immunity and inflammation as well as stemness. In this review, we summarize the let-7-dependent and let-7-independent mechanism regulated by Lin28, focusing on its relation with tumor hallmarks in breast cancer, and subsequently discuss our present knowledge of Lin28 to develop a molecular-based therapeutic strategy against breast cancer.
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