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Abstract
Objective This study aims to explore circ_0058063 effect on multiple myeloma cells malignant phenotype and its feasible mechanism. Methods We selected 47 cases of multiple myeloma tissues and 47 cases of normal bone marrow tissues and then used RT-qPCR method to test circ_0058063 and miR-635 expression in the tissues. Myeloma cells RPMI8226 were transfected with si-circ_0058063, miR-635 mimic, and si-circ_0058063 + anti-miR-635, respectively. Then, we adopt CCK-8 method, flow cytometry method, and Transwell and western blot methods to detect the influences of knockdown of circ_0058063 or miR-635 overexpression on RPMI8226 cell proliferation, apoptosis, migration, and invasion and also Ki-67, Bax, Bcl-2, MMP-2, and MMP-9 protein expression. The dual luciferase reporter gene assay experiment proved that it has regulatory relationship between circ_0058063 and miR-635. Results circ_0058063 expression of multiple myeloma was higher than that in normal bone marrow tissue (P < 0.05), while miR-635 expression was lower than that in normal bone marrow tissue (P < 0.05). Knockdown of circ_0058063 or overexpression of miR-635 could reduce proliferation capacity, migration, invasion cell quantities, and Ki-67, MMP-2, MMP-9, and Bcl-2 protein expression (P < 0.05), while increasing apoptosis rate together with Bax protein expression (P < 0.05). circ_0058063 targets to negatively regulate miR-635, while knocking down miR-635 reverses the influences of knocking down circ_0058063 on RPMI8226 proliferation, apoptosis, migration, and invasion. Conclusion circ_0058063 expression increased in multiple myeloma tissues. Knocking down its expression may inhibit myeloma proliferation, migration, and invasion by targeting and upregulating miR-635 and also promote cell apoptosis. As for multiple myeloma treatment, circ_0058063/miR-635 may provide new molecular targets.
Highlights
Multiple myeloma is known as a kind of malignant plasma cell disease
Exclusion criteria: patients with other malignant tumors; patients with chronic diseases such as hypertension and diabetes. Another 47 h matrix metalloproteinase 2 (MMP-2) healthy individuals who underwent bone marrow aspiration and had no abnormalities in bone marrow function at our institution during the same period were included as controls, who were 24 men and 23 women; their average age is about 59.46 ± 8.76 years old. e ethics committee of our hospital has approved this research, and the patients voluntarily signed the informed consent
Discussion Circular RNA (circRNA) has a closed circular and stable structure and is conservative. circRNA can play the role of miRNA molecular sponge, regulate miRNA target gene expression and affect the process of cell proliferation, differentiation, and apoptosis, and affect the occurrence and development of multiple myeloma and other tumors [8]
Summary
Multiple myeloma is known as a kind of malignant plasma cell disease. In recent years, its incidence has been increasing year by year, and it is showing a younger trend [1]. MiR-635 is situated on chromosome 17q and has a reduced expression in nonsmall cell lung cancer [6] and osteosarcoma tumor [7]; it can inhibit proliferation, migration of tumor cells, and other malignant phenotypes, thereby acting as a tumor suppressor gene in tumors Until now, it is still unknown whether miR-635 has influence on the occurrence and development of myeloma. Erefore, this study took myeloma RPMI8226 cells as the research object and mainly explored the effect of circ_0058063/miR-635 axis on malignant phenotype (proliferation, apoptosis, migration, and invasion) of myeloma cells and the possible mechanism, aiming to provide targeted molecular therapy of myeloma a new target Since myeloma RPMI8226 cells have been extensively studied, their research characteristics have long been confirmed. erefore, this study took myeloma RPMI8226 cells as the research object and mainly explored the effect of circ_0058063/miR-635 axis on malignant phenotype (proliferation, apoptosis, migration, and invasion) of myeloma cells and the possible mechanism, aiming to provide targeted molecular therapy of myeloma a new target
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