LAT1 and ASCT2 Related microRNAs as Potential New Therapeutic Agents against Colorectal Cancer Progression

Abstract

The development and progression of colorectal cancer (CRC) have been associated with genetic and epigenetic alterations and more recently with changes in cell metabolism. Amino acid transporters are key players in tumor development, and it is described that tumor cells upregulate some AA transporters in order to support the increased amino acid (AA) intake to sustain the tumor additional needs for tumor growth and proliferation through the activation of several signaling pathways. LAT1 and ASCT2 are two AA transporters involved in the regulation of the mTOR pathway that has been reported as upregulated in CRC. Some attempts have been made in order to develop therapeutic approaches to target these AA transporters, however none have reached the clinical setting so far. MiRNA-based therapies have been gaining increasing attention from pharmaceutical companies and now several miRNA-based drugs are currently in clinical trials with promising results. In this review we combine a bioinformatic approach with a literature review in order to identify a miRNA profile with the potential to target both LAT1 and ASCT2 with potential to be used as a therapeutic approach against CRC.

Energy Substrate Transporters in High-Grade Ovarian Cancer: Gene Expression and Clinical Implications

“…A vast number of studies have demonstrated that the expression of amino acid transporters LAT1 and ASCT2 is enhanced in tumor tissues, e.g., colorectal cancer, suggesting a crucial role of amino acid supply in fulfilling the high proliferation rate in cancer cells [ 66 ]. However, scarce information is available concerning the relationship of amino acid transporter expression with cell growth in human ovarian cancer.…”

LINC01006 and miR-3199 Serve as Novel Markers of Poor Prognosis in Colon Cancer and Regulate Cell Proliferation, Migration and Invasion

“… 20 In colorectal cancer, miR-3199 was screened as a downregulated DEmiRNA. 21 As common differentially expressed lncRNA and miRNA in colon cancer, 22 , 23 the functions and functional mechanism of LINC01006 and miR-3199 in colon cancer have not been revealed.…”

Detection of Adenocarcinoma of the Colon on 18F-Fluciclovine PET/CT

“…One subtype of treatment-resistant colorectal cancer, KRAS mutated, is associated with increased expression of ASCT2 8 . Both ASCT2 and LAT1 are investigational targets for future therapies, including microRNA treatment 9 . Both prostate and colorectal cancers have been linked to dietary and genetic factors with ongoing research in these areas 10 …”

“…8 Both ASCT2 and LAT1 are investigational targets for future therapies, including microRNA treatment. 9 Both prostate and colorectal cancers have been linked to dietary and genetic factors with ongoing research in these areas. 10…”