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SILENCE OF LONG NONCODING RNA MALAT1 BY RNA INTERFERENCE INHIBITS PROLIFERATION AND INDUCES APOPTOSIS IN MULTIPLE MYELOMA
Author(s): ,
Hui Liu
Affiliations:
Hematology,Shengjing Hospital of China Medical University,Shenyang,China
,
Zimu Gong
Affiliations:
Hematology,Shengjing hospital of China Medical University,Shenyang, China;Hematopathology,The University of Texas, MD Anderson Cancer Center,Houston,United States
Wei Yang
Affiliations:
Hematology,Shengjing Hospital of China Medical University,Shenyang,China
(Abstract release date: 05/18/17) EHA Library. Chi Z. 05/18/17; 182653; PB1939
Zuofei Chi
Zuofei Chi
Contributions
Abstract

Abstract: PB1939

Type: Publication Only

Background
Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by abnormal proliferation of monoclonal plasma cells in bone marrow leading to various end-organ damages. Altered long non-coding RNAs (lncRNAs) levels can result in aberrant expression of gene products that may contribute to cancer biology. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), an evolutionarily highly conserved mRNA-like lncRNA was originally identified with high expression in metastatic non-small-cell lung cancer and reported to be up-regulated in many other cancers. However, the function of MALAT1 in MM remains unknown.

Aims
Our study aimed to evaluate the role of MALAT1 on proliferation as well as apoptosis in MM cells in vitro and tumorigenic ability in vivo, following transfection with MALAT1‑specific short hairpin RNA (shRNA) expression plasmids.

Methods
Levels of MALAT1 in human myeloma cell lines were detected by real-time polymerase chain reaction (RT-PCR) analysis. The effects of MALAT1 shRNA in MM were investigated in vitro and in vivo.

Results
We found that MALAT1 was high expressing in RPMI8226 and U266 cells. Silencing of MALAT1 by shRNA significantly inhibited the proliferation through cell cycle arrest at G1 phase and induced apoptosis, which was closely associated with activation of caspase-3/-9, downregulation of Bcl-2 and upregulation of Bax. Study in vivo revealed that silencing of MALAT1 delayed the tumor growth and led to apoptosis in mice bearing myeloma xenograft.

Conclusion
MALAT1 may serve as a promising novel therapeutic target in human MM. Notably, the inhibition of MALAT1 by shRNA may prove to be an effective genetic therapeutic strategy for MM treatment.

Session topic: 13. Myeloma and other monoclonal gammopathies - Biology

Keyword(s): Myeloma

Abstract: PB1939

Type: Publication Only

Background
Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by abnormal proliferation of monoclonal plasma cells in bone marrow leading to various end-organ damages. Altered long non-coding RNAs (lncRNAs) levels can result in aberrant expression of gene products that may contribute to cancer biology. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), an evolutionarily highly conserved mRNA-like lncRNA was originally identified with high expression in metastatic non-small-cell lung cancer and reported to be up-regulated in many other cancers. However, the function of MALAT1 in MM remains unknown.

Aims
Our study aimed to evaluate the role of MALAT1 on proliferation as well as apoptosis in MM cells in vitro and tumorigenic ability in vivo, following transfection with MALAT1‑specific short hairpin RNA (shRNA) expression plasmids.

Methods
Levels of MALAT1 in human myeloma cell lines were detected by real-time polymerase chain reaction (RT-PCR) analysis. The effects of MALAT1 shRNA in MM were investigated in vitro and in vivo.

Results
We found that MALAT1 was high expressing in RPMI8226 and U266 cells. Silencing of MALAT1 by shRNA significantly inhibited the proliferation through cell cycle arrest at G1 phase and induced apoptosis, which was closely associated with activation of caspase-3/-9, downregulation of Bcl-2 and upregulation of Bax. Study in vivo revealed that silencing of MALAT1 delayed the tumor growth and led to apoptosis in mice bearing myeloma xenograft.

Conclusion
MALAT1 may serve as a promising novel therapeutic target in human MM. Notably, the inhibition of MALAT1 by shRNA may prove to be an effective genetic therapeutic strategy for MM treatment.

Session topic: 13. Myeloma and other monoclonal gammopathies - Biology

Keyword(s): Myeloma

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