Title:Targeting miRNAs for Pancreatic Cancer Therapy
VOLUME: 20 ISSUE: 33
Author(s):Min Shi, DachengXie, Yong Gaod and Keping Xie
Affiliation:Department of Gastroenterology, Hepatology & Nutrition, Unit 1466, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Keywords:miRNA, FOXM1, pancreatic cancer, transcription, invasion, metastasis, therapy.
Abstract:Pancreatic cancer (PC) is the fourth leading cause of cancer-related deaths in the United States and has a median 5-year survival
rate less than 5%. Although surgery offers the best chance for a cure for pancreatic cancer, less than 20% of patients are eligible for
potentially curative resection, because in most cases, the cancer has already spread locally or to distant organs at diagnosis, precluding resection.
MicroRNAs (miRNAs) are small noncoding, endogenous, single-stranded RNAs that are pivotal regulators of posttranscriptional
gene expression. Extensive studies of miRNAs over the past several years have revealed that the expression of miRNAs is frequently deregulated
in pancreatic cancer patients and that this deregulation contributes to the pathogenesis and aggressiveness of the disease. Currently,
investigators are studying the use of miRNAs as diagnostic and/or prognostic biomarkers and therapeutic tools for pancreatic cancer.
Rapid discovery of many miRNA targets and their relevant pathways has contributed to the development of miRNA-based therapeutics.
In particular, the transcription factor Forkhead box M1 (FOXM1) is overexpressed in the majority of cancer patients, including those
with pancreatic cancer. This overexpression is implicated to have a role in tumorigenesis, progression, and metastasis. This important role
of FOXM1 affirms its usefulness in therapeutic interventions for pancreatic cancer. In this review, we summarize the current knowledge
and concepts concerning the involvement of miRNAs and FOXM1 in pancreatic cancer development and describe the roles of the
miRNA-FOXM1 signaling pathway in pancreatic cancer initiation and progression. Additionally, we describe some of the technical challenges
in the use of the miRNA-FOXM1 signaling pathway in pancreatic cancer treatment.
