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

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 upregulating CDC5L.

Pan-Cancer Transcriptome and Immune Infiltration Analyses Reveal the Oncogenic Role of Far Upstream Element-Binding Protein 1 (FUBP1)

“…Interestingly, Cdc5L is a pre-mRNA splicing factor consisting of Prp19/Pso4, Plrg 1 and Spf27 that modulates the expression of genes involved in mitosis and the ATR-mediated cell cycle checkpoint ( Zhang et al, 2009 ; Mu et al, 2014 ). This transcription factor has been reported to promote tumorigenesis in various cancers, such as bladder cancer, ovarian cancer, prostate cancer, and multiple myeloma ( Li et al, 2018 ; Chunmei et al, 2020 ; Liu et al, 2020 ; Ziwei et al, 2020 ). The most enriched GO items suggest the remarkable role of RNA splicing in the mechanism of FUBP1 across different cancer types, and the small-molecule splicing modulators that are currently in clinical trials offer a promising approach to cancer therapy.…”

Role of annexin A family in tumorigenesis and chemoresistance of gastric cancer

“…ANXA7 is an important member of the annexin A family. Several studies demonstrated that the aberrant expression of ANXA7 plays a major role in the occurrence and development of a variety of tumors, such as hepatocellular carcinoma [91], multiple myeloma [92], glioma [93], prostate cancer [94], and breast cancer [95]. In 2008, a study reported that a striking correlation between ANXA7 expression and the differentiated degree of GC, and the ANXA7 expression was higher in intestinal-type than in diffuse-type tumor.…”

Computational prediction of CRISPR-impaired non-coding regulatory regions

“…Another candidate is the NT5C2 gene, which is known to confer treatment resistance against thiorubin in acute lymphocytic leukemias [41]. For ANXA7 it was shown that resistance in different cancer types has been observed [43,44].…”