Abstract
Gastrointestinal (GI) cancer represents a major global health problem due to its aggressive characteristics and poor prognosis. Despite the progress achieved in the development of treatment regimens, the clinical outcomes and therapeutic responses of patients with GI cancer remain unsatisfactory. Chemoresistance arising throughout the clinical intervention is undoubtedly a critical barrier for the successful treatment of GI cancer. However, the precise mechanisms associated with chemoresistance in GI cancer remain unclear. In the past decade, accumulating evidence has indicated that circular RNAs (circRNAs) play a key role in regulating cancer progression and chemoresistance. Notably, circRNAs function as molecular sponges that sequester microRNAs (miRNAs) and/or proteins, and thus indirectly control the expression of specific genes, which eventually promote or suppress drug resistance in GI cancer. Therefore, circRNAs may represent potential therapeutic targets for overcoming drug resistance in patients with GI cancer. This review comprehensively summarizes the regulatory roles of circRNAs in the development of chemoresistance in different GI cancers, including colorectal cancer, gastric cancer and esophageal cancer, as well as deciphers the underlying mechanisms and key molecules involved. Increasing knowledge of the important functions of circRNAs underlying drug resistance will provide new opportunities for developing efficacious therapeutic strategies against GI cancer.
Highlights
Gastrointestinal (GI) cancers are among the most important causes of cancer-related death worldwide and mainly include colorectal cancer (CRC), gastric cancer (GC) and esophageal cancer (EC) (Wang D.-K. et al, 2021)
Chemoresistance has become a major hurdle undermining the efficacy of cancer chemotherapy
It is essential to elucidate the mechanisms associated with cancer chemoresistance, which will accelerate the development of improved therapeutic approaches for cancer
Summary
Gastrointestinal (GI) cancers are among the most important causes of cancer-related death worldwide and mainly include colorectal cancer (CRC), gastric cancer (GC) and esophageal cancer (EC) (Wang D.-K. et al, 2021). Conventional treatments, including chemotherapy, radiotherapy and surgery, have been the mainstays of cancer therapy (Buckley et al, 2020) These therapeutic approaches have limitations and lead to unsatisfactory clinical outcomes, as evidenced by the high mortality rate of patients with GI cancers (D’Eliseo and Velotti, 2016; Hsu et al, 2020). CircHIPK3 acted as a molecular sponge for miR-637 to stimulate the downstream signal transducer and activator of transcription 3 (STAT3)/B-cell lymphoma-2 (Bcl-2)/Beclin 1 signaling cascade in CRC cells (Zhang et al, 2019). This event resulted in the suppression of autophagic cell death and enhanced oxaliplatin (OXA) resistance in CRC cells. Future directions are suggested to better apprehend their exact roles and their usefulness as therapeutic targets
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