SRC3 expressed in BMSCs promotes growth and migration of multiple myeloma cells by regulating the expression of Cx43

International Journal of Oncology
Jie JinJin Wang

Abstract

Interactions between bone marrow stromal cells (BMSCs) and multiple myeloma cells significantly contribute to the progression of multiple myeloma (MM). However, little is known about the molecular mechanisms that regulate these interactions. Connexin-43 (Cx-43) has been implicated in the interplay between BMSCs and MM cells. In this study, we hypothesized that the steroid receptor co-activator-3 (SRC3) expressed in BMSCs regulates the expression of Cx-43 to promote the proliferation and migration of myeloma cells. To address this, we co-cultured a human multiple myeloma cell line, RPMI-8226 transfected with either control BMSCs or sh-SRC3-BMSCs. We found that knocking down SRC3 expression in BMSCs inhibited the proliferation and migration of RPMI-8226 cells. In addition, we found that co-culturing RPMI 8266 cells with BMSCs increased Cx43 expression, while knocking down SRC3 expression in BMSCs decreased Cx43 expression. Moreover, our work revealed that SRC3 in BMSCs regulates Cx43 expression via the mitogen-activated protein kinase (MAPK) pathway. To validate this result in vivo, we knocked down SRC3 expression in BMSCs in nude mice and found that tumor growth and cell apoptosis were significantly decreased. In addition, mice ...Continue Reading

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Citations

Nov 27, 2019·Acta Biochimica Et Biophysica Sinica·Jie JinJin Wang
Jun 19, 2019·Asian-Australasian Journal of Animal Sciences·Hyungkuen KimSung-Jo Kim
Feb 6, 2020·Frontiers in Pharmacology·Raúl Lagos-CabréLisette Leyton
Oct 16, 2020·Journal of Receptor and Signal Transduction Research·Jiuyang JiangTiewa Zhang

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Methods Mentioned

BETA
ISS
transfection
Protein Assay
PCR

Software Mentioned

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