Abstract
The development of Colorectal Cancer (CRC) follows a sequential progression from adenoma to the carcinoma. Therefore, opportunities exist to interfere with the natural course of disease development and progression. Dysregulation of microRNAs (miRNAs) in cancer cells indirectly results in higher levels of messenger RNA (mRNA) specific to tumour promoter genes or tumour suppressor genes. This narrative review aims to provide a comprehensive review of the literature about the manipulation of oncogenic or tumour suppressor miRNAs in colorectal cancer cells for the purpose of development of anticancer therapies. A literature search identified studies describing manipulation of miRNAs in colorectal cancer cells in vivo and in vitro. Studies were also included to provide an update on the role of miRNAs in CRC development, progression and diagnosis. Strategy based on restoration of silenced miRNAs or inhibition of over expressed miRNAs has opened a new area of research in cancer therapy. In this review article different techniques for miRNA manipulation are reviewed and their utility for colorectal cancer therapy has been discussed in detail. Restoration of normal equilibrium for cancer related miRNAs can result in inhibition of tumour growth, apoptosis, blocking of invasion, angiogenesis and metastasis. Furthermore, drug resistant cancer cells can be turned into drug sensitive cells on alteration of specific miRNAs in cancer cells. MiRNA modulation in cancer cells holds great potential to replace current anticancer therapies. However, further work is needed on tissue specific delivery systems and strategies to avoid side effects.
Highlights
Colorectal cancer (CRC) is the third most common neoplasm worldwide
This review aims to provide the update on the role of miRNAs in CRC development and the diagnostic utility of circulating miRNAs
The literature search identified 48 original scientific studies and review articles in which some or all of the outcomes of interest were reported. 18 additional articles and web-based information sites were selected to provide a general background to miRNA and colorectal neoplasia. 36 additional studies were included to supplement the information in colorectal cancer development, detection of circulating miRNAs, and principles of miRNA therapy, design and delivery
Summary
Colorectal cancer (CRC) is the third most common neoplasm worldwide. According to the International Agency for Research on Cancer, approximately 1.24 million new cases of CRC were detected worldwide in 2008 [1]. The incidence of CRC is on the rise in developing countries, southern and eastern Europe [2,3,4]. Contrary to the current trend in Europe, the incidence of CRC in the USA has fallen in the last two decades [5]. The lifetime risk for developing CRC [6] in men is 1 in 16 whereas in women it is 1 in 20 (National Statistics, UK). The development of CRC follows the sequential progression from adenoma to carcinoma [7]. The initial genetic alteration results in adenoma formation in which cells exhibit
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