The Emerging Role of TYRO3 as a Therapeutic Target in Cancer

Smart, Sherri K.; Vasileiadi, Eleana; Wang, Xiaodong; DeRyckere, Deborah; Graham, Douglas K.

doi:10.3390/cancers10120474

Cited by 75 publications

(69 citation statements)

References 146 publications

(324 reference statements)

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“…To further figure out the mechanism of circRNA-miRNA-mRNA network, we idetified TYRO3 as one direct target of miR-338-3pin CRC cells. TYRO3 is a protein tyrosine kinase and previous literatures have revealed that TYRO3 is significantly increased in various cancers, promoting cancer cell proliferation and metastasis and enhancing the drug resistance, making it a potential therapeutic target [27,28]. In addition, TYRO3 was also confirmed to play vital roles in the regulation of EMT process, chemical resistance, liver metastasis, cell proliferation and apoptosis in colorectal cancer as an oncogene [29].…”

Section: Discussionmentioning

confidence: 95%

circRAE1 promotes colorectal cancer cell migration and invasion through modulating miR-338-3p/TYRO3 axis

Chen

et al. 2020

Preprint

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Background: Growing evidences have revealed that long non-coding RNAs (lncRNAs) including circular RNAs (circRNAs) involve in numerous carcinogenesis. However, the roles of circRNAs in the cancer biology of colorectal cancer (CRC) remain vague. Methods: qRT-PCR and western-blot were used to detecte the circRAE1 levels in CRC tissues and CRC cell lines. Cell proliferation, migration and invasion were detected using wound healing assays, and transwell assays. The interaction between circRAE1 and miR-338-3p and TRYO3 was confirmed by dual-luciferase reporter assays. Results: We uncovered that a novel circRNA Hsa_circ_0060967 (also known as circRAE1) was remarkably increased in CRC tissues, and high circRAE1 level was positively associated with advanced tumor stage, lymph node metastasis, and tumor size. Loss-of-function assay indicated that circRAE1 accelerated cell proliferation, migration and invasion. Besides, miR-338-3p , lowly expressed in CRC tissues and CRC cell lines. dual-luciferase reporter assays showed that circRAE1 could sponge miR-338-3p, which targeted TRYO3 in CRC cells. Furthermore, overexpression of circRAE1 could recue the impaired migration and invasion triggered by miR-338-3p mimics or si-TYRO3 in CRC cells and vice versa. Conclusion : We figured out the network of circRAE1, miR-338-3p, and TYRO3 in CRC cells and revealed that increased circRAE1 served as an oncogene through sponging miR-338-3p, resulting in upregulated TYRO3 expression, which suggested that circRAE1 would be a potential therapeutic target and diagnostic marker for CRC treatment.

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Section: Discussionmentioning

confidence: 95%

circRAE1 promotes colorectal cancer cell migration and invasion through modulating miR-338-3p/TYRO3 axis

Chen

et al. 2020

Preprint

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“…TYRO3 is a protein tyrosine kinase. Previous literature has shown that TYRO3 is signi cantly increased in various cancers, and it promotes cancer cell proliferation and metastasis and enhances drug resistance, and thus is a potential therapeutic target [27,28]. In addition, TYRO3 was also con rmed to play vital roles in regulating the expression of EMT markers, chemical resistance, liver metastasis, cell proliferation, and apoptosis in CRC as an oncogene [29].…”

Section: Discussionmentioning

confidence: 95%

circRAE1 promotes colorectal cancer cell migration and invasion through modulating miR-338-3p/TYRO3 axis

Chen

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Growing evidences have revealed that long non-coding RNAs (lncRNAs) including circular RNAs (circRNAs) involve in numerous carcinogenesis. However, the roles of circRNAs in the cancer biology of colorectal cancer (CRC) remain vague. Methods: qRT-PCR and western-blot were used to detecte the circRAE1 levels in CRC tissues and CRC cell lines.,Cell proliferation, migration and invasion were detected using wound healing assays, and transwell assays. The interaction between circRAE1 and miR-338-3p and TRYO3 was confirmed by dual-luciferase reporter assays. Results: We uncovered that a novel circRNA Hsa_circ_0060967 (also known as circRAE1) was remarkably increased in CRC tissues, and high circRAE1 level was positively associated with advanced tumor stage, lymph node metastasis, and tumor size. Loss-of-function assay indicated that circRAE1 accelerated cell proliferation, migration and invasion. Besides, miR-338-3p , lowly expressed in CRC tissues and CRC cell lines. dual-luciferase reporter assays showed that circRAE1 could sponge miR-338-3p, which targeted TRYO3 in CRC cells. Furthermore, overexpression of circRAE1 could recue the impaired migration and invasion triggered by miR-338-3p mimics or si-TYRO3 in CRC cells and vice versa. Conclusion : we figured out the network of circRAE1, miR-338-3p, and TYRO3 in CRC cells and revealed that increased circRAE1 served as an oncogene through sponging miR-338-3p, resulting in upregulated TYRO3 expression, which suggested that circRAE1 would be a potential therapeutic target and diagnostic marker for CRC treatment.

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“…Tyro3TK was initially discovered as a therapeutic target in tumors [36]. Increasing studies have focused on their critical role in autoimmune diseases [37,38].…”

Section: Discussionmentioning

confidence: 99%

CD14+CD16- monocytes are the main precursors of osteoclasts in rheumatoid arthritis via expressing Tyro3TK

Xue

Zhu

et al. 2020

Preprint

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Background: Monocytes as precursors of osteoclasts in rheumatoid arthritis (RA) are well demonstrated, while monocyte subsets in osteoclast formation are still controversial. Tyro3 tyrosine kinase (Tyro3TK) is a member of the receptor tyrosine kinase family involved in immune homeostasis, the role of which in osteoclast differentiation was reported recently. This study aimed to compare the osteoclastic capacity of CD14+CD16+ and CD14+CD16- monocytes in RA and determine the potential involvement of Tyro3TK in their osteoclastogenesis.Methods: Osteoclasts were induced from CD14+CD16+ and CD14+CD16- monocyte subsets isolated from healthy control (HC) and RA patients in vitro and evaluated by tartrate-resistant acid phosphatase (TRAP) staining. Then, the expression of Tyro3TK on CD14+CD16+ and CD14+CD16- monocyte subsets in peripheral blood of RA, osteoarthritis (OA) patients, and HC were evaluated by flow cytometry and qPCR, and their correlation with RA patient clinical and immunological features was analyzed. The role of Tyro3TK in CD14+CD16- monocytes-mediated osteoclastogenesis was further investigated by osteoclast differentiation assay with Tyro3TK blockade.Results: The results revealed that CD14+CD16- monocytes were the primary source of osteoclasts. Compared with HC and OA patients, the expression of Tyro3TK on CD14+CD16- monocytes in RA patients was significantly upregulated, and positively correlated with the disease manifestations, such as IgM level, tender joint count and the disease activity score. Moreover, anti-Tyro3TK antibody could inhibit Gas6-mediated osteoclast differentiation from CD14+CD16- monocytes in a dose-dependent manner.Conclusions: These findings indicate that elevated Tyro3TK on CD14+CD16- monocytes serves as a critical signal for osteoclast differentiation in RA.

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The Emerging Role of TYRO3 as a Therapeutic Target in Cancer

Cited by 75 publications

References 146 publications

circRAE1 promotes colorectal cancer cell migration and invasion through modulating miR-338-3p/TYRO3 axis

circRAE1 promotes colorectal cancer cell migration and invasion through modulating miR-338-3p/TYRO3 axis

circRAE1 promotes colorectal cancer cell migration and invasion through modulating miR-338-3p/TYRO3 axis

CD14+CD16- monocytes are the main precursors of osteoclasts in rheumatoid arthritis via expressing Tyro3TK

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