Role of microRNAs in the resistance of colorectal�cancer to chemoradiotherapy (Review)

Abstract

Abstract. Colorectal cancer (CRC) is among the main tumor-related causes of death worldwide. The fact that the majority of the patients develop resistance to chemoradiotherapy (CRT) is a major obstacle for the treatment of CRC. In order to develop more effective treatment strategies, it is crucial to elucidate the mechanisms underlying the development of resistance to CRT. Several studies have recently indicated the regulatory effects of microRNAs (miRNAs) in response to antitumor agents. For example, miR-34a attenuates the chemoresistance of colon cancer to 5-FU by inhibiting E2F3 and SIRT1. The miR-34a mimic MRX34 is the first synthetic miRNA to have been entered into clinical trials. miR-21 prevents tumor cell stemness, invasion and drug resistance, which are required for the development of CRC. These findings suggest that miRNAs represent a focus in the research of novel cancer treatments aimed at sensitizing cancer cells to chemotherapeutic drugs. The aim of the present study was to review the functions of miRNAs and investigate the roles of miRNAs in CRC radioresistance or chemoresistance. Furthermore, the potential of including miRNAs in therapeutic strategies and using them as molecular biomarkers for predicting radiosensitivity and chemosensitivity was discussed.

Long non-coding RNA HOTAIR knockdown enhances radiosensitivity through regulating microRNA-93/ATG12 axis in colorectal cancer

“…However, the existence and development of radioresistance is a great obstacle in the treatment of CRC 4,5 . Over the past decades, accumulating non-coding RNAs including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been found to be key regulators or potential biomarkers in tumor initiation, progression, and radioresistance of CRC [5][6][7] .…”

COUP-TFII in Health and Disease

“…MiR-34a is a tumor suppressor miRNA: In colorectal cancer its expression is usually downregulated, often because of TGF-β action or long non-coding RNA acting as sponge for the miRNA [195,196]. Key features of miR-34a are the inhibition of cell migration and its chemosensitizer role in colorectal cancer [197,198]. COUP-TFII directly induces the expression of miR-21 in TGF-β-treated cells, resulting in the downregulation of SMAD7 whereas it reduces miR-34a [161,162]; hence, modulating miR-21a and miR-34a, COUP-TFII strengthen its action as tumor oncogene and induces EMT in colorectal cancer.…”

Collapsin response mediator protein 4 enhances radio-sensitivity through calcium-mediated cell signaling

“…During cancer treatment, radiotherapy is used in conjunction with surgery to reduce the risk of recurrence and metastasis [1,2]. Although radiotherapy may constitute a suitable treatment strategy for many cancer patients, the persistence of radiation-resistant tumor cells often poses a signi cant obstacle to an effective radiation-based therapy and leads to poor prognosis [3,4]. Thus, understanding the mechanisms governing radiation resistance is a signi cant step toward enhancing the utility of radiotherapy.…”