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Review
. 2021 Oct 8:26:892-926.
doi: 10.1016/j.omtn.2021.10.004. eCollection 2021 Dec 3.

The role of non-coding RNAs in chemotherapy for gastrointestinal cancers

Fatemeh Dashti  1   2 , Seyed Mohammad Ali Mirazimi  1   2 , Nikta Rabiei  3 , Reza Fathazam  3 , Negin Rabiei  3 , Haleh Piroozmand  4 , Massoud Vosough  5 , Neda Rahimian  6 , Michael R Hamblin  7   8 , Hamed Mirzaei  9
Affiliations
Review

The role of non-coding RNAs in chemotherapy for gastrointestinal cancers

Fatemeh Dashti et al. Mol Ther Nucleic Acids. .

Abstract

Gastrointestinal (GI) cancers, including colorectal, gastric, hepatic, esophageal, and pancreatic tumors, are responsible for large numbers of deaths around the world. Chemotherapy is the most common approach used to treat advanced GI cancer. However, chemoresistance has emerged as a critical challenge that prevents successful tumor elimination, leading to metastasis and recurrence. Chemoresistance mechanisms are complex, and many factors and pathways are involved. Among these factors, non-coding RNAs (ncRNAs) are critical regulators of GI tumor development and subsequently can induce resistance to chemotherapy. This occurs because ncRNAs can target multiple signaling pathways, affect downstream genes, and modulate proliferation, apoptosis, tumor cell migration, and autophagy. ncRNAs can also induce cancer stem cell features and affect the epithelial-mesenchymal transition. Thus, ncRNAs could possibly act as new targets in chemotherapy combinations to treat GI cancer and to predict treatment response.

Keywords: gastrointestinal cancers; non-coding RNAs; response to chemotherapy.

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Conflict of interest statement

M.R.H. declares the following potential conflicts of interest. Scientific Advisory Boards: Transdermal Cap, Inc, Cleveland, OH, USA; BeWell Global, Inc, Wan Chai, Hong Kong; Hologenix, Inc, Santa Monica, CA, USA; LumiThera, Inc, Poulsbo, WA, USA; Vielight, Toronto, ON, Canada; Bright Photomedicine, Sao Paulo, Brazil; Quantum Dynamics, LLC, Cambridge, MA, USA; Global Photon, Inc, Bee Cave, TX, USA; Medical Coherence, Boston, MA, USA; NeuroThera, Newark, DE, USA; JOOVV, Inc, Minneapolis-St. Paul, MN, USA; AIRx Medical, Pleasanton, CA, USA; FIR Industries, Inc, Ramsey, NJ, USA; UVLRx Therapeutics, Oldsmar, FL, USA; Ultralux UV, Inc, Lansing, MI, USA; Illumiheal and PetThera, Shoreline, WA, USA; MB Lasertherapy, Houston, TX, USA; ARRC LED, San Clemente, CA, USA; Varuna Biomedical Corp, Incline Village, NV, USA; Niraxx Light Therapeutics, Inc, Boston, MA, USA. Consulting: Lexington International, LLC, Boca Raton, FL, USA; USHIO Corp, Japan; Merck KGaA, Darmstadt, Germany; Philips Electronics Nederland BV, Eindhoven, the Netherlands; Johnson & Johnson, Inc, Philadelphia, PA, USA; Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany. Stockholdings: Global Photon, Inc, Bee Cave, TX; Mitonix, Newark, DE. The remaining authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
The biogenesis process of different types of ncRNAs (A) RNA polymerase II (RNA Pol II) transcribes most miRNA genes and generates pre-miRNAs longer than 200 nt, composed of a hairpin structure containing the miRNA sequence. The pre-miRNAs are cleaved in the nucleus by RNase III enzyme Drosha into nearly 70-nt-long pre-miRNAs with a stem-loop motif. The pre-miRNAs are exported to the cytoplasm and are then cleaved by another RNase III enzyme called Dicer. Eventually, the ∼22 miRNA duplex is loaded into the RNA-induced silencing complex (RISC) where the mature single-stranded miRNA binds to complementary mRNA targets. (B) lncRNAs have been shown to be transcribed from genomic sequences. lncRNAs are classified into various categories, including promoter-related lncRNAs, enhancer-related lncRNAs, intronic and exonic lncRNAs, antisense lncRNAs, and long intergenic lncRNAs. (C) Numerous circRNAs are obtained from the pre-mRNAs, depending on the spliceosomes. circRNAs are classified into different types, including intron circRNAs, exon circRNAs, and extron-intron circRNAs. Read-through circRNA (rt-circRNA) is a new type of circRNA (dotted line).
Figure 2
Figure 2
An overview of the role of lncRNAs in chemoresistance (A) lncRNA-associated pathways in HCC. (B) lncRNA-associated pathways in breast cancer. (C) lncRNA-associated pathways in lung cancer.
See this image and copyright information in PMC

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