Identification of a selective inhibitor of human monocarboxylate transporter 4

Background: Colorectal cancer (CRC) is currently the third most common cancer type in males and the second most occurring in females. The role of microRNA (miRNA) in the development of colorectal cancer is not fully elucidated. Therefore, understanding the mechanistic interaction between miRNA and their target oncogenes may hold great importance as a possible target for interventional anticancer therapy. Aims: To identify miRNAs that are part of the regulating pathway of Monocarboxylate Transporter-4 (MCT4) and Vascular Endothelial Growth Factor (VEGF) oncogenes. Study Design: We used publicly available prediction tools (e.g. TargetScan, MicroCosm, PicTar, and DIANA-microT-CDS) to identify the possible miRNA that target the two oncogenes. Methodology: We used the GeneMania database to visualize the network and verify gene names and remove ambiguity and duplications. Furthermore, we used miRTarBase database to identify experimentally validated targets which we used to further confirm miRNA-oncogene relationships. Finally, we utilized miR-Mfold web-tool to further visualize the circular structures and the simulated miR-1 and miR-206 targeting arrangements. Results: We found two putative miRNA (miR-1 and miR-206) that may downregulate MCT4 coded by SLC16A3 gene and VEGF which is coded by VEGF gene. We found relationships between the validated target genes of miR-1 and miR-206 through GeneMania which we extracted from the literature. And we elucidated the proposed structure of these two miRNAs through miR-Mfold web-tool. Conclusion: Our results elucidated a novel regulation pathway in CRC cells and may suggest a potential therapeutic approach for CRC therapy. MiR-1 and miR-206 may help cells go to apoptosis and inhibit the angiogenesis of colorectal cancer cells by down-regulation of MCT4 and VEGF proteins in tumor tissues.

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Effects of streptozotocin-induced diabetes on markers of skeletal muscle metabolism and monocarboxylate transporter 1 to monocarboxylate transporter 4 transporters

Metabolism ◽

10.1053/meta.2002.33343 ◽

2002 ◽

Vol 51 (7) ◽

pp. 807-813 ◽

Cited By ~ 22

Author(s):

Guillaume Py ◽

Karen Lambert ◽

Ollivier Milhavet ◽

Nicolas Eydoux ◽

Christian Pr[eacute]faut ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Metabolism ◽

Monocarboxylate Transporter ◽

Skeletal Muscle Metabolism ◽

Monocarboxylate Transporter 1 ◽

Streptozotocin Induced Diabetes ◽

Monocarboxylate Transporter 4

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Monocarboxylate Transporter 4 Is a Therapeutic Target in Non-small Cell Lung Cancer with Aerobic Glycolysis Preference

Molecular Therapy — Oncolytics ◽

10.1016/j.omto.2020.06.012 ◽

2020 ◽

Vol 18 ◽

pp. 189-201 ◽

Cited By ~ 1

Author(s):

Ting-Chun Kuo ◽

Kuo-Yen Huang ◽

Shuenn-Chen Yang ◽

Sean Wu ◽

Wei-Chia Chung ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Therapeutic Target ◽

Aerobic Glycolysis ◽

Small Cell ◽

Monocarboxylate Transporter ◽

Small Cell Lung ◽

Monocarboxylate Transporter 4

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Intratumoral reciprocal expression of monocarboxylate transporter 4 and glypican-3 in hepatocellular carcinomas

BMC Research Notes ◽

10.1186/s13104-019-4778-y ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 1

Author(s):

Kenji Yorita ◽

Akinobu Ohno ◽

Takahiro Nishida ◽

Kazuhiro Kondo ◽

Toshihiko Ohtomo ◽

...

Keyword(s):

Prognostic Factors ◽

Expression Patterns ◽

Japanese Patients ◽

Monocarboxylate Transporter ◽

Two Factors ◽

Gpc3 Expression ◽

History Of ◽

Reciprocal Expression ◽

Immunohistochemical Analyses ◽

Monocarboxylate Transporter 4

Abstract Objective We previously reported the identification of monocarboxylate transporter 4 (MCT4) and glypican-3 (GPC3) as prognostic factors for hepatocellular carcinoma (HCC), which are now considered significant poor prognostic factors for the disease. This study aimed to clarify the detailed interaction of these two factors in HCC to improve our understanding of aggressive HCC phenotypes. A total of 225 Japanese patients with HCC from our previous study were subjected to immunohistochemical analyses. Results The number of MCT4-positive (MCT4+) HCC cases was 47 (21%), and most MCT4+ HCC showed high GPC3 expression (94%, 44/47 cases). In 44 MCT4+/GPC3+ HCC cases, intratumoral heterogeneity of GPC3 or MCT4 expression was further evaluated. We observed reciprocal (inverse), synergistic, mixed reciprocal and synergistic, or irrelevant interaction of MCT4 and GPC3 expression in 29 (66%), 5 (11%), 1 (2%), and 9 cases (21%), respectively. The cases exhibiting reciprocal expression of both markers tended to have cirrhosis without a history of neoadjuvant therapy. In summary, although MCT4+ HCC cases are mostly GPC3+, intratumoral expression patterns of MCT4 and GPC3 are frequently reciprocal each other, suggesting that dual targeting of MCT4 and GPC3 may achieve a better antitumor effect for MCT4+ HCC cases.

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