<p>MicroRNA-761 targets FGFR1 to suppress the malignancy of osteosarcoma by deactivating PI3K/Akt pathway</p>

Abstract

Purpose: has been reported to be deregulated in many types of human cancers and play important roles in cancer genesis and progression. However, the biological roles of miR-761 in osteosarcoma (OS) and the underlying mechanisms remain largely unknown. Methods: The expression of miR-761 in OS tissues and cell lines was analyzed using RT-qPCR. A series of gain-of-function tests were performed, and status of malignancy was evaluated on basis of proliferation, migration, invasion, and apoptosis using different assays to determine the regulatory roles of miR-761 in OS cells in vivo and in vitro. Notably, the mechanisms underlying the action of miR-761 in the pathogenesis of OS were investigated using bioinformatic analysis, luciferase reporter assay, RT-qPCR and Western blotting. Results: The results showed that miR-761 expression was decreased in OS tissues and cell lines and is closely correlated with clinical stage and distant metastasis in OS patients. Patients with OS having low miR-761 expression showed worse prognosis compared to OS patients with high miR-761 expression. Restoring the miR-761 expression level decreased OS cell proliferation, migration, and invasion in vitro; promoted cell apoptosis in vitro; and impaired tumor growth in vivo. In addition, fibroblast growth factor receptor 1 (FGFR1) was found as a direct target gene of miR-761 in OS cells. Furthermore, silencing FGFR1 expression stimulated the tumor-suppressing roles of miR-761 upregulation in OS cells, whereas the activity of miR-761 overexpression in OS cells was abolished by the restoration of FGFR1 expression. Moreover, restoration of miR-761 expression deactivated the PI3K/ Akt pathway in vitro and in vivo. Conclusion: These results suggest that miR-761 plays anti-cancer roles in OS by directly targeting FGFR1 and deactivating the PI3K/Akt pathway. The newly identified miR-761/ FGFR1/PI3K/Akt pathway partially illustrates the mechanism of OS pathogenesis and presents a novel candidate therapeutic target for antitumor therapy.

Long non‐coding RNA HOTAIR/microRNA‐761 sponge regulates PPME1 and further influences cell biological functions in thyroid carcinoma

“…We also found that miR‐761 and PPME1 were negatively correlated after analyzing by linear regression. miR‐761 may suppress osteosarcomas and affect their biological function, such as proliferation, apoptosis, invasion and metastasis 24 . Consistent with our results, Lv et al highlighted the tumor‐ suppressing abilities of miR‐761.…”

CircIL4R activates the PI3K/AKT signaling pathway via the miR-761/TRIM29/PHLPP1 axis and promotes proliferation and metastasis in colorectal cancer

“…Previous studies have reported that miR-761 can attenuate the malignant progression of CRC and deactivate the PI3K/Akt signaling pathway in osteosarcoma [ 33 , 34 ]. Thus, to further elucidate whether circIL4R activates the PI3K/AKT pathway by interacting with miR-761, rescue experiments were performed by cotransfecting miR-761 mimics or inhibitor with the circIL4R overexpression plasmid or corresponding siRNA.…”

“…In the current study, we observed that circIL4R can act as a sponge to competitively bind with miR-761, as verified by RNA pull-down, dual-luciferase reporter, and FISH assays. miR-761 was previously reported to be a tumor suppressor that was downregulated in several cancers and to deactivate the PI3K/AKT signaling pathway [ 33 , 34 , 54 , 55 ]. In agreement with previous reports, our data revealed that miR-761 expression could inhibit the proliferation and metastasis of CRC cells and was downregulated in CRC tissues and cells.…”

Proanthocyanidin B2 inhibits proliferation and induces apoptosis of osteosarcoma cells by suppressing the PI3K/AKT pathway

“…The PI3K/AKT pathway is an important intracellular signalling pathway that plays an indispensable role in the regulation of various cell biological behaviours, such as cell proliferation and apoptosis 33,45,46 . Most studies have indicated that the PI3K/AKT pathway is active in osteosarcoma cells, and its inhibition can reduce OS cell proliferation, invasion and induce apoptosis 15,47 .…”