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Editor’s note iNature is China’s largest academic official account.
It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
.
iNature multiple myeloma (MM) is an incurable plasma cell malignant tumor in the bone marrow, which is characterized by chromosomal instability (CIN), which can lead to the acquisition of heterogeneity, and the progression of multiple myeloma, Resistance and relapse
.
On October 7, 2021, Nanjing University of Traditional Chinese Medicine Yang Ye, Gu Xiaosong and Gu Chunyan jointly published a research paper entitled "BUB1B and circBUB1B_544aa aggravate multiple myeloma malignancy through evoking chromosomal instability" in Signal Transduction and Targeted Therapy (IF=18.
19).
This study clarified that the expression of BUB1B is significantly increased in MM patients and is closely related to adverse results
.
Overexpression of BUB1B promoted cell proliferation and induced drug resistance in vitro and in vivo, while the targeted gene BUB1B eliminated this effect
.
Mechanism studies have shown that the forced expression of BUB1B can cause CIN, which leads to adverse MM results mainly through phosphorylation of CEP170
.
Interestingly, the study found that there is a circBUB1B_544aa containing the catalytic center of BUB1B kinase, which is translated by the circular RNA of BUB1B
.
The increase of circBUB1B_544aa in MM peripheral blood samples is closely related to the adverse outcome of MM, and it plays a synergistic effect with BUB1B in inducing CIN
.
In addition, MM cells can secrete circBUB1B_544aa and interfere with MM microenvironment cells in the same way as the full-length BUB1B protein
.
Interestingly, the BUB1B siRNA targeting the kinase catalytic center of BUB1B and circBUB1B_544aa significantly inhibited MM malignancies in vitro and in vivo
.
In general, BUB1B and circBUB1B_544aa are promising prognostic and therapeutic targets for MM
.
Multiple myeloma (MM) is a molecular and cytogenetic heterogeneous hematological malignancy that originates in the bone marrow (BM)
.
Although targeted drugs such as immunomodulators and proteasome inhibitors have greatly improved the prognosis of MM patients for decades, MM is still life-threatening and incurable
.
It is well known that genetic and epigenetic aberrations, clonal heterogeneity and clonal evolution play an indispensable role in the progression, drug resistance and relapse of MM
.
However, the molecular basis of the pathogenesis of MM is still not fully understood
.
Chromosomal instability (CIN) accelerates the development of MM malignancies and drug resistance, leading to treatment failure and recurrence, which limits the effectiveness of most current therapies
.
Therefore, the identification of new molecules and signaling pathways involved in the relationship between CIN and MM is essential
.
BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) is a conserved multifunctional protein, which is essential for the function of the mitotic spindle checkpoint and the correction of kinetochore-microtubule attachment
.
The inactivation of BUB1B has been shown to cause spindle checkpoints and severe chromosome segregation defects
.
According to reports, the widespread elevation of BUB1B is closely related to the high cell proliferation and poor clinical outcomes of various cancers including MM
.
By using sequence gene expression profile (GEP) in MM patient samples, it was found that BUB1B induced CIN in MM
.
However, the exact mechanism of BUB1B-mediated MM promotion is still unclear
.
The article pattern (picture from Signal Transduction and Targeted Therapy) MM is highly dependent on the BM microenvironment, and the interaction between the corresponding cells of MM and other cells in BM is of great significance to the development of MM therapy
.
Circular RNAs are single-stranded closed RNA molecules that are derived from the reverse splicing of precursor mRNA to form a covalently closed loop
.
In particular, circRNA has been elucidated to play a key role in the occurrence, development, invasion and drug resistance of cancer
.
Importantly, circRNAs have an important impact on the tumor microenvironment through cell-to-cell communication, which is attributed to their abundance in exosomes and human body fluids
.
Therefore, circRNA is now regarded as a promising cancer biomarker
.
In this study, not only the role of BUB1B in the proliferation and drug resistance of MM cells was characterized, but it was also determined that the circular form of the BUB1B gene encodes a new 544 amino acid protein in MM cells called circBUB1B_544aa
.
Interestingly, circBUB1B_544aa contains the BUB1B kinase catalytic center, which may be secreted into the BM microenvironment, and its potential role in MM has been studied in vitro and in vivo
.
The study also used clinical samples and patient data to evaluate the relationship between BUB1B or circBUB1B_544aa expression and patient prognosis
.
Finally, the study demonstrated the new downstream targets of BUB1B and circBUB1B_544aa
.
These findings provide important insights into the functional importance of BUB1B and circBUB1B_544aa as promising prognostic and therapeutic targets for MM
.
Reference message: https://
It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
.
iNature multiple myeloma (MM) is an incurable plasma cell malignant tumor in the bone marrow, which is characterized by chromosomal instability (CIN), which can lead to the acquisition of heterogeneity, and the progression of multiple myeloma, Resistance and relapse
.
On October 7, 2021, Nanjing University of Traditional Chinese Medicine Yang Ye, Gu Xiaosong and Gu Chunyan jointly published a research paper entitled "BUB1B and circBUB1B_544aa aggravate multiple myeloma malignancy through evoking chromosomal instability" in Signal Transduction and Targeted Therapy (IF=18.
19).
This study clarified that the expression of BUB1B is significantly increased in MM patients and is closely related to adverse results
.
Overexpression of BUB1B promoted cell proliferation and induced drug resistance in vitro and in vivo, while the targeted gene BUB1B eliminated this effect
.
Mechanism studies have shown that the forced expression of BUB1B can cause CIN, which leads to adverse MM results mainly through phosphorylation of CEP170
.
Interestingly, the study found that there is a circBUB1B_544aa containing the catalytic center of BUB1B kinase, which is translated by the circular RNA of BUB1B
.
The increase of circBUB1B_544aa in MM peripheral blood samples is closely related to the adverse outcome of MM, and it plays a synergistic effect with BUB1B in inducing CIN
.
In addition, MM cells can secrete circBUB1B_544aa and interfere with MM microenvironment cells in the same way as the full-length BUB1B protein
.
Interestingly, the BUB1B siRNA targeting the kinase catalytic center of BUB1B and circBUB1B_544aa significantly inhibited MM malignancies in vitro and in vivo
.
In general, BUB1B and circBUB1B_544aa are promising prognostic and therapeutic targets for MM
.
Multiple myeloma (MM) is a molecular and cytogenetic heterogeneous hematological malignancy that originates in the bone marrow (BM)
.
Although targeted drugs such as immunomodulators and proteasome inhibitors have greatly improved the prognosis of MM patients for decades, MM is still life-threatening and incurable
.
It is well known that genetic and epigenetic aberrations, clonal heterogeneity and clonal evolution play an indispensable role in the progression, drug resistance and relapse of MM
.
However, the molecular basis of the pathogenesis of MM is still not fully understood
.
Chromosomal instability (CIN) accelerates the development of MM malignancies and drug resistance, leading to treatment failure and recurrence, which limits the effectiveness of most current therapies
.
Therefore, the identification of new molecules and signaling pathways involved in the relationship between CIN and MM is essential
.
BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) is a conserved multifunctional protein, which is essential for the function of the mitotic spindle checkpoint and the correction of kinetochore-microtubule attachment
.
The inactivation of BUB1B has been shown to cause spindle checkpoints and severe chromosome segregation defects
.
According to reports, the widespread elevation of BUB1B is closely related to the high cell proliferation and poor clinical outcomes of various cancers including MM
.
By using sequence gene expression profile (GEP) in MM patient samples, it was found that BUB1B induced CIN in MM
.
However, the exact mechanism of BUB1B-mediated MM promotion is still unclear
.
The article pattern (picture from Signal Transduction and Targeted Therapy) MM is highly dependent on the BM microenvironment, and the interaction between the corresponding cells of MM and other cells in BM is of great significance to the development of MM therapy
.
Circular RNAs are single-stranded closed RNA molecules that are derived from the reverse splicing of precursor mRNA to form a covalently closed loop
.
In particular, circRNA has been elucidated to play a key role in the occurrence, development, invasion and drug resistance of cancer
.
Importantly, circRNAs have an important impact on the tumor microenvironment through cell-to-cell communication, which is attributed to their abundance in exosomes and human body fluids
.
Therefore, circRNA is now regarded as a promising cancer biomarker
.
In this study, not only the role of BUB1B in the proliferation and drug resistance of MM cells was characterized, but it was also determined that the circular form of the BUB1B gene encodes a new 544 amino acid protein in MM cells called circBUB1B_544aa
.
Interestingly, circBUB1B_544aa contains the BUB1B kinase catalytic center, which may be secreted into the BM microenvironment, and its potential role in MM has been studied in vitro and in vivo
.
The study also used clinical samples and patient data to evaluate the relationship between BUB1B or circBUB1B_544aa expression and patient prognosis
.
Finally, the study demonstrated the new downstream targets of BUB1B and circBUB1B_544aa
.
These findings provide important insights into the functional importance of BUB1B and circBUB1B_544aa as promising prognostic and therapeutic targets for MM
.
Reference message: https://
