ANXA7 promotes the cell cycle, proliferation and cell adhesion-mediated drug resistance of multiple myeloma cells by up-regulating CDC5L.

Haiyan Liu,Yuou Sha,Dan Guo,Yuwen Jiang,Yijing Jiang,Jie Zhang,Hongming Huang,Ling Lu,Lemin Hong,Chenlu Zhang

doi:10.18632/aging.103326

Haiyan Liu, Yuou Sha + Show 8 more

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https://doi.org/10.18632/aging.103326

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Abstract

This study aimed to investigate whether annexin A7 (ANXA7) could promote the cell cycle, proliferation and cell adhesion-mediated drug resistance (CAM-DR) of multiple myeloma (MM) cells by up-regulating cell division cycle 5-like (CDC5L). As a result, ANXA7 expression was increased in the serum of MM patients and the expression of ANXA7 and CDC5L was also increased in MM cell lines. ANXA7 overexpression promoted the proliferation and cycle of U266 and RPMI8226 cells. The expression of proliferation cell nuclear antigen (PCNA), KI67, cyclin dependent kinase 1 (CDK1) and cyclinB1 in transfected cells was consistent with the changes of proliferation and cell cycle. In co-culture system of BMSC cells and MM cells, expression of CD44, ICAM1 and VCAM1 in MM cells was increased, which was further increased by ANXA7 overexpression. Bortezomib could increase the apoptosis of U266 and RPMI8226 cells. In co-culture system of BMSC cells and MM cells, the promotion effects of bortezomib on apoptosis of MM cells was decreased, which was further suppressed by ANXA7 overexpression. The above effects exerted by ANXA7 overexpression could be reversed by ANXA7 interference. Moreover, ANXA7 was proved to be combined with CDC5L. CDC5L interference could inhibit the promotion effects of ANXA7 overexpression on proliferation and cell cycle and inhibition effects of ANXA7 overexpression on apoptosis of MM cells treated with bortezomib in co-culture system. In conclusion, ANXA7 could promote the cell cycle, proliferation and CAM-DR of MM cells by up-regulating CDC5L.

Highlights

Multiple myeloma (MM) is a widespread and incurable disease caused by the malignant proliferation and abnormal accumulation of clonal marrow plasma cells [1]
annexin A7 (ANXA7) overexpression promoted the proliferation of U266 and RPMI8226 cells (Figure 2C), which demonstrated by colony formation assay (Figure 2D)
We aimed to investigate whether ANXA7 interference could promote cell cycle arrest in G2/M phase through cell division cycle 5-like (CDC5L) to inhibit proliferation of MM cells and reduce cell adhesion-mediated drug resistance

Summary

Introduction

Multiple myeloma (MM) is a widespread and incurable disease caused by the malignant proliferation and abnormal accumulation of clonal marrow plasma cells [1]. MM incidence has been increasing year by year and the age of onset has become younger, accounting for about 13% of hematological malignancies and 1% of all malignancies [2, 3]. Most clinical treatments for MM have been chemoradiotherapy, autologous/allogeneic stem cell transplantation and targeted drug therapy to improve the quality of life and prolong the survival of patients, but the occurrence of acquired drug resistance makes MM still incurable, which has become one of the biggest challenges for MM [4,5,6]. In order to bring new hope to MM patients, we must work harder to study the complex pathogenesis of MM and find more appropriate therapies for early diagnosis of MM

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