Promotion or remission: a role of noncoding RNAs in colorectal cancer resistance to anti-EGFR therapy

Abstract

Anti-epidermal-growth-factor-receptor (EGFR) monoclonal antibodies (mAbs) are of great significance for RAS and BRAF wild-type metastatic colorectal cancer (mCRC) patients. However, the generation of primary and secondary resistance to anti-EGFR mAbs has become an important factor restricting its efficacy. Recent studies have revealed that non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are implicated in anti-EGFR antibodies resistance, affecting the sensitivity of CRC cells to Cetuximab and Panitumumab. This paper briefly reviewed the research advance of the expression, signaling network and functional mechanism of ncRNAs related to anti-EGFR mAbs resistance in CRC, as well as their relationship with clinical prognosis and the possibility of therapeutic targets. In addition, some ncRNAs that are involved in the regulation of signaling pathways or genes related to anti-EGFR resistance, but need to be further verified by resistance experiments were also included in this review, thereby providing more ideas and basis for ncRNAs as CRC prognostic markers and anti-EGFR therapy sensitizers.

The Clinical Significance of MicroRNAs in Colorectal Cancer Signaling Pathways: A Review

“…41 A series of investigations in the field revealed the extensive implication of microRNAs in regulation of EGFR signaling that significantly enhanced our detailed understanding of intestinal carcinogenesis. 42 Two of the most important EGFR-related microRNA tumor-suppressor genes are mir-143 and mir-145. Expression analyses have shown that these molecules are significantly diminished in cells of colorectal tumor origin compared with normal epithelium.…”

Targeting epigenetic regulators to overcome drug resistance in cancers

“…Recent studies have described the effects of non-coding RNAs on drug resistance in colorectal and lung cancer, including lncRNA, miRNA, and circRNAs, indicating that ncRNAs can be used as biomarkers to predict drug resistance. [97][98][99] Fatemeh Najafi et al also focused on the involvement of miR-424 and miR-631 in the regulation of tumor resistance and sensitivity. 100 EMT is an important mechanism by which tumors develop drug resistance, and HaShem khanbabaei et al summarized the relationship between non-coding RNAs and EMT in cancers, suggesting that ncRNAs might serve as important regulators in tumor resistance.…”

Long non-coding RNA signature in colorectal cancer: research progression and clinical application

“…that may regulate genes primarily enriched in the Rap1 and RAS signaling pathways and result in a poorer prognosis. Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab and panitumumab) are important for patients with wildtype RAS and BRAF metastatic CRC, high expression of lncRNAs (MIR100HG, UCA1, CRART16, SLCO4A1-AS1 and TTN-AS1) in CRC enhances the sensitivity of CRC cells to cetuximab and panitumumab [108].…”