microRNA-377-3p inhibits osteosarcoma progression by targeting CUL1 and regulating Wnt/β-catenin signaling pathway.

Abstract

OBJECTIVE:

Emerging studies highlight the crucial effects of microRNAs on cancer initiation and malignant progression of various tumors. This study focused on the biological effect of miR-377-3p on CUL1 and epithelial-mesenchymal transition (EMT) and Wnt/β-catenin pathways in osteosarcoma (OS).

METHODS:

We performed quantitative real-time polymerase chain reaction (qRT-PCR) to analyze miR-377-3p and CUL1 expression levels in OS tissues and MG-63 cells. Then, cell counting kit (CCK)-8 and Transwell assay were used to examine the functions of miR-377-3p in OS cell growth and metastasis abilities. Meanwhile, luciferase reporter assay was used to validate CUL1 as direct target of miR-377-3p. qRT-PCR and Western blot were then carried out to detect the impact of miR-377-3p on EMT and Wnt/β-catenin pathways. Tumor xenograft models were established to further examine the effects of miR-377-3p on OS tumorigenesis in vivo.

RESULTS:

miR-377-3p downregulation was frequently identified in OS tissues and cells, which was associated with worse prognosis of OS patients. Functional experiments showed miR-377-3p restoration could dramatically repress OS cell growth and migration by regulation of EMT and Wnt/β-catenin pathways. Moreover, luciferase reporter assay revealed that CUL1 acted as a functional target of miR-377-3p. Additionally, the elevated CUL1 expressions in OS tissues also indicated poor prognosis of OS patients. Furthermore, the OS tumor growth was also obviously inhibited by miR-377-3p overexpression in vivo.

CONCLUSIONS:

Collectively, all the above findings revealed that miR-377-3p exerted anti-OS functions via CUL1 and EMT and Wnt/β-catenin pathways. These results may contribute to the development of clinical OS treatment.

• Authors: K Liang, L Liao, Q Liu, Q Ouyang, L Jia, G Wu
• Journal: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico (Clin Transl Oncol) Vol. 23 Issue 11 Pg. 2350-2357 (Nov 2021) ISSN: 1699-3055 [Electronic] Italy
• PMID: 34133001 (Publication Type: Journal Article)
• Copyright: © 2021. Federación de Sociedades Españolas de Oncología (FESEO).

Chemical References

• Cullin 1
• Cullin Proteins
• MIRN377 microRNA, human
• MicroRNAs
• Luciferases

Topics

• Animals
• Bone Neoplasms (metabolism, mortality, pathology)
• Cell Line, Tumor
• Cullin Proteins (metabolism)
• Disease Progression
• Down-Regulation
• Epithelial-Mesenchymal Transition
• Genes, Reporter
• Heterografts
• Humans
• Luciferases (genetics)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (metabolism)
• Neoplasm Transplantation
• Osteosarcoma (metabolism, mortality, pathology, secondary)
• Prognosis
• Reverse Transcriptase Polymerase Chain Reaction
• Wnt Signaling Pathway