Molecular immunology · 2025
Knockdown of RRBP1 regulates endoplasmic reticulum stress to mitigate malignant progression and suppress bortezomib resistance of multiple myeloma cells by inhibiting GRP78 expression.
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Wang Jie, Jia Haipeng, Lv Sulong, Zhang Xiaofen, Duan Yanchao
Аннотация
BACKGROUND: Ribosome binding protein 1 (RRBP1) was reported to play a regulatory role in certain cancers. It was related to poor prognosis and drug resistance in multiple myeloma (MM), but its mechanism has not been reported before. Hence, its effect and the specific mechanism on MM cells were explored.
METHODS: The expression levels of RRBP1 and Glucose-regulated protein 78 (GRP78) in MM tissues were detected by immunohistochemical assay. The expression levels of mRNA and protein were analyzed by qRT-PCR and western blot, respectively. MM cell viability and proliferation were tested by CCK-8 assay. Flow cytometry was used to detect cell apoptosis. Transwell assay was carried out to explore cell migration and invasion.
RESULTS: The expression levels of RRBP1 and GRP78 were upregulated in MM tissues and MM cells. Transfection of sh-RRBP1 weakened the proliferation, migration and invasion abilities of MM cells. Knockdown of RRBP1 dropped GRP78 expression and diminished endoplasmic reticulum stress in MM cells. Moreover, Tunicamycin-induced apoptosis of MM cells was enhanced by RRBP1 knockdown. Compared to the control group, inhibition of RRBP1 expression increased the drug sensitivity of bortezomib-resistant MM cells. In addition, overexpression of GRP78 partially repealed the effectiveness of sh-RRBP1 on MM cells.
CONCLUSION: Our study elucidated the inhibitory effect of RRBP1 knockdown on MM cells, which suggested that RRBP1 might be a novel target for the therapy against MM.
METHODS: The expression levels of RRBP1 and Glucose-regulated protein 78 (GRP78) in MM tissues were detected by immunohistochemical assay. The expression levels of mRNA and protein were analyzed by qRT-PCR and western blot, respectively. MM cell viability and proliferation were tested by CCK-8 assay. Flow cytometry was used to detect cell apoptosis. Transwell assay was carried out to explore cell migration and invasion.
RESULTS: The expression levels of RRBP1 and GRP78 were upregulated in MM tissues and MM cells. Transfection of sh-RRBP1 weakened the proliferation, migration and invasion abilities of MM cells. Knockdown of RRBP1 dropped GRP78 expression and diminished endoplasmic reticulum stress in MM cells. Moreover, Tunicamycin-induced apoptosis of MM cells was enhanced by RRBP1 knockdown. Compared to the control group, inhibition of RRBP1 expression increased the drug sensitivity of bortezomib-resistant MM cells. In addition, overexpression of GRP78 partially repealed the effectiveness of sh-RRBP1 on MM cells.
CONCLUSION: Our study elucidated the inhibitory effect of RRBP1 knockdown on MM cells, which suggested that RRBP1 might be a novel target for the therapy against MM.