MicroRNA expression profile associated with response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients

Abstract

BackgroundRectal cancer accounts for approximately one third of all colorectal cancers (CRC), which belong among leading causes of cancer deaths worldwide. Standard treatment for locally advanced rectal cancer (cT3/4 and/or cN+) includes neoadjuvant chemoradiotherapy with fluoropyrimidines (capecitabine or 5-fluorouracil) followed by radical surgical resection. Unfortunately, a significant proportion of tumors do not respond enough to the neoadjuvant treatment and these patients are at risk of relapse. MicroRNAs (miRNAs) are small non-coding RNAs playing significant roles in the pathogenesis of many cancers including rectal cancer. MiRNAs could present the new predictive biomarkers for rectal cancer patients.MethodsWe selected 20 patients who underwent neoadjuvant chemoradiotherapy for advanced rectal cancer and whose tumors were classified as most sensitive or resistant to the treatment. These two groups were compared using large-scale miRNA expression profiling.ResultsExpression levels of 8 miRNAs significantly differed between two groups. MiR-215, miR-190b and miR-29b-2* have been overexpressed in non-responders, and let-7e, miR-196b, miR-450a, miR-450b-5p and miR-99a* have shown higher expression levels in responders. Using these miRNAs 9 of 10 responders and 9 of 10 non-responders (p < 0.05) have been correctly classified.ConclusionsOur pilot study suggests that miRNAs are part of the mechanisms that are involved in response of rectal cancer to the chemoradiotherapy and that miRNAs may be promising predictive biomarkers for such patients. In most miRNAs we identified (miR-215, miR-99a*, miR-196b, miR-450b-5p and let-7e), the connection between their expression and radioresistance or chemoresistance to inhibitors of thymidylate synthetase was already established.

Targeting HER3 with miR-450b-3p suppresses breast cancer cells proliferation

“…22 Recently higher expression of miR-450b-5p has been reported to be associated with better response to neoadjuvant chemoradiotherapy in the locally advanced rectal cancer patients; however, the mechanisms remained unknown. 23 Our results provided the new clues that miR-450b-3p interacts with HER3 mRNA at 3′ UTR to repress HER3 expression and to modulate HER3 mediated PI3K/AKT pathway. To our knowledge, this is the first article to discuss the regulation of HER3 by miR-450b-3p in breast cancers.…”

A Three-microRNA Signature Predicts Responses to Platinum-Based Doublet Chemotherapy in Patients with Lung Adenocarcinoma

“…Interestingly, a recent study shows that the expression of miR196b is upregulated in patients with rectal adenocarcinoma that respond to neoadjuvant chemoradiotherapy (capecitabine or 5-fluorouracil), which supports the findings of the present study (42). However, preliminary experiments examining the exogenous expression of the three miRNAs in LADC cell lines did not show increased sensitivity to a platinum agent, cisplatin (CDDP).…”

Tumor suppressor miR-29c regulates radioresistance in lung cancer cells

“…Our findings revealed a set of 50 miRNAs differentially expressed (Table 1 and Figure 2(a)) that are either upregulated (16 miRNAs) or downregulated (34 miRNAs). Among them, miR-197, 26 miR-29c, 27 and miR-21* 28 have been established as prognostic and risk factors in lung cancer, whereas miR-450a, 24 miR-96, 25 and miR-29c have been related to the response to radiotherapy in certain types of cancer, including lung cancer. 16,22,27 Most of the miRNAs identified have not been previously described in the context of radioresistance.…”