School of Medicine and Health Sciences Poster Presentations

Title

Implication of the Long Non-Coding RNA Crnde in Multiple Myeloma

Poster Number

121

Document Type

Poster

Status

Medical Student

Abstract Category

Basic Biomedical Sciences

Keywords

multiple myeloma, lncRNA

Publication Date

Spring 2018

Abstract

Multiple myeloma (MM) is an incurable malignancy of antibody-secreting plasma cells, with a wide clinical and prognostic spectrum, even within groups bearing the same primary initiating cytogenetic event, for which the molecular mechanisms responsible remain poorly understood. Long non-coding RNAs (lncRNAs; broadly defined as non-coding RNAs of > 200 nt) have recently emerged as an important class of regulatory molecules and are increasingly implicated in tumorigenesis and cancer progression. However, currently their contribution to the progression and clinical variability of MM is largely unknown.

In order to identify lncRNAs potentially implicated in the etiology of MM, we have taken a data mining approach to compare the expression profile of lncRNAs between CD138+ plasmocytes from healthy individuals with those from MM patients. Patients were stratified according to the presence of the t(4;14) or t(11;14) translocations and a third group bearing neither of these cytogenetic events. This analysis revealed 110 lncRNAs that are differentially expressed in CD138+ plasma cells from newly diagnosed MM patients compared to control subjects. A candidate to emerge from this analysis is Colorectal Neoplasia Differentially Expressed (CRNDE), a lncRNA implicated in other hematological malignancies and diverse solid tumors, by promoting growth and inhibiting apoptosis potentially via a physical association with epigenetic modifying complexes (PRC2 and CoREST). Our findings suggest that CRNDE is involved in MM disease progression, causing progression from the pre-malignant MGUS to the smoldering myeloma stage and reaching highest levels in overt symptomatic myeloma. Further, survival analysis indicates that high CRNDE expression is associated with poor overall survival, in particular in high risk t(4;14)+ myeloma patients. To directly test the role of CRNDE in MM and to investigate downstream oncogenic pathways, we are using CRISPR/Cas9 to delete the major nuclear and cytoplasmic isoforms of CRNDE in MM cell lines.

Results indicate that the deletion of CRNDE exerts a dose-dependent repressive effect on myeloma cell growth, supporting its involvement in MM disease progression. CRISPER/Cas9 deletion is being carried out in both a t(4;14) and non t(4;14) context. We also investigated the effect of CRNDE deletions on the sensitivity of MM cells to therapeutic agents and the interaction of CRNDE with Polycomb group proteins.

Overall, our results suggest that CRNDE plays a role in MM disease progression and outcome. This work has the potential to translate into clinical benefit, notably by providing a useful biomarker of MM and novel therapeutic strategies based on lncRNAs.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Open Access

1

This document is currently not available here.

Share

COinS
 

Implication of the Long Non-Coding RNA Crnde in Multiple Myeloma

Multiple myeloma (MM) is an incurable malignancy of antibody-secreting plasma cells, with a wide clinical and prognostic spectrum, even within groups bearing the same primary initiating cytogenetic event, for which the molecular mechanisms responsible remain poorly understood. Long non-coding RNAs (lncRNAs; broadly defined as non-coding RNAs of > 200 nt) have recently emerged as an important class of regulatory molecules and are increasingly implicated in tumorigenesis and cancer progression. However, currently their contribution to the progression and clinical variability of MM is largely unknown.

In order to identify lncRNAs potentially implicated in the etiology of MM, we have taken a data mining approach to compare the expression profile of lncRNAs between CD138+ plasmocytes from healthy individuals with those from MM patients. Patients were stratified according to the presence of the t(4;14) or t(11;14) translocations and a third group bearing neither of these cytogenetic events. This analysis revealed 110 lncRNAs that are differentially expressed in CD138+ plasma cells from newly diagnosed MM patients compared to control subjects. A candidate to emerge from this analysis is Colorectal Neoplasia Differentially Expressed (CRNDE), a lncRNA implicated in other hematological malignancies and diverse solid tumors, by promoting growth and inhibiting apoptosis potentially via a physical association with epigenetic modifying complexes (PRC2 and CoREST). Our findings suggest that CRNDE is involved in MM disease progression, causing progression from the pre-malignant MGUS to the smoldering myeloma stage and reaching highest levels in overt symptomatic myeloma. Further, survival analysis indicates that high CRNDE expression is associated with poor overall survival, in particular in high risk t(4;14)+ myeloma patients. To directly test the role of CRNDE in MM and to investigate downstream oncogenic pathways, we are using CRISPR/Cas9 to delete the major nuclear and cytoplasmic isoforms of CRNDE in MM cell lines.

Results indicate that the deletion of CRNDE exerts a dose-dependent repressive effect on myeloma cell growth, supporting its involvement in MM disease progression. CRISPER/Cas9 deletion is being carried out in both a t(4;14) and non t(4;14) context. We also investigated the effect of CRNDE deletions on the sensitivity of MM cells to therapeutic agents and the interaction of CRNDE with Polycomb group proteins.

Overall, our results suggest that CRNDE plays a role in MM disease progression and outcome. This work has the potential to translate into clinical benefit, notably by providing a useful biomarker of MM and novel therapeutic strategies based on lncRNAs.