Let-7 as biomarker, prognostic indicator, and therapy for precision medicine in cancer

被引:226
作者
Chirshev, Evgeny [1 ]
Oberg, Kerby C. [2 ]
Ioffe, Yevgeniya J. [3 ]
Unternaehrer, Juli J. [4 ]
机构
[1] Loma Linda Univ, Dept Basic Sci, Div Anat, Loma Linda, CA 92350 USA
[2] Loma Linda Univ, Div Anat & Pediat Pathol, Loma Linda, CA 92350 USA
[3] Loma Linda Univ, Sch Med, Gynecol & Obstet, Loma Linda, CA USA
[4] Loma Linda Univ, Dept Basic Sci, Div Biochem, 11085 Campus St,Mortensen Hall 219, Loma Linda, CA 92354 USA
关键词
microRNA; Cancer; Gene regulation; Biomarker; Therapeutics; Tumor suppressor; EPITHELIAL OVARIAN-CANCER; CELL-CYCLE PROGRESSION; STEM-LIKE CELLS; BREAST-CANCER; SELF-RENEWAL; HEPATOCELLULAR-CARCINOMA; MESENCHYMAL TRANSITION; TUMOR-SUPPRESSOR; CIRCULATING MICRORNAS; HEMATOPOIETIC STEM;
D O I
10.1186/s40169-019-0240-y
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Abnormal regulation and expression of microRNAs (miRNAs) has been documented in various diseases including cancer. The miRNA let-7 (MIRLET7) family controls developmental timing and differentiation. Let-7 loss contributes to carcinogenesis via an increase in its target oncogenes and stemness factors. Let-7 targets include genes regulating the cell cycle, cell signaling, and maintenance of differentiation. It is categorized as a tumor suppressor because it reduces cancer aggressiveness, chemoresistance, and radioresistance. However, in rare situations let-7 acts as an oncogene, increasing cancer migration, invasion, chemoresistance, and expression of genes associated with progression and metastasis. Here, we review let-7 function as tumor suppressor and oncogene, considering let-7 as a potential diagnostic and prognostic marker, and a therapeutic target for cancer treatment. We explain the complex regulation and function of different let-7 family members, pointing to abnormal processes involved in carcinogenesis. Let-7 is a promising option to complement conventional cancer therapy, but requires a tumor specific delivery method to avoid toxicity. While let-7 therapy is not yet established, we make the case that assessing its tumor presence is crucial when choosing therapy. Clinical data demonstrate that let-7 can be used as a biomarker for rational precision medicine decisions, resulting in improved patient survival.
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页数:14
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