Abstract 282P
Background
Multiple Myeloma (MM) is second most common hematological malignancy characterized by uncontrolled proliferation of abnormal plasma cells in bone marrow. microRNAs are newly emerged nowadays for their involvement in post-transcriptional regulation of certain genes. Earlier, we reported overexpression of an extracellular matrix protein, Versican (VCAN) in MM especially in the stroma but its involvement in disease pathogenesis has not been reported yet. Hence, we studied the role of VCAN via its regulation by microRNAs on myeloma pathogenesis.
Methods
The molecular expression of VCAN was investigated in myeloma cell lines (RPMI8226 & U266). The antagomirs of microRNAs (miR-144 and miR-199) were then transfected into myeloma cells to investigate the effect on VCAN expression along with the effect on proliferation, apoptosis, migration and invasion of myeloma cells. In addition, signaling pathways affected by the inhibition of miR-144 and miR-199 were also identified. The functional regulation of VCAN by miR-144 and miR-199 was also confirmed by reporter luciferase assay in which VCAN 3’UTR was transfected to the myeloma cells.
Results
The expression of VCAN was found at minimal level in both the myeloma cells. The transfection of antagomirs of miR-144 and miR-199 significantly enhanced the transcript and protein levels of VCAN in myeloma cells. Further, myeloma cells parameters found to be altered in favor of disease progression such as cell proliferation, migration and invasion increased with simultaneous inhibition of apoptosis. In addition, antagomirs mediated upregulation of VCAN promote myeloma progression via activation of FAK/STAT3 signaling. Moreover, transfection of wild type VCAN 3’UTR resulted in significant decrease in luciferase activity which got restored by mutating the binding site of microRNAs.
Conclusions
miR-144 and mir-199 antagomirs mediated over-expression of VCAN promoted the myeloma pathogenesis in vitro with downstream activation of FAK and STAT3 signaling. These findings, therefore, affirm the translational importance of microRNAs which could be adopted as a mean for targeting VCAN and might emerge as an effective therapy for better management of MM in clinical settings in future.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
AIIMS, New Delhi, India.
Funding
All India Institute of Medical Sciences, Council of Scientific and Industrial Research.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
27P - The prognostic value of neutrophil to lymphocyte ratio (NLR) and 18F-FDG PET SUV in breast cancer patients underwent neoadjuvant chemotherapy
Presenter: Soong June Bae
Session: Poster display session
Resources:
Abstract
28P - Accuracy of core biopsy in predicting pathologic complete response in the breast in patients with complete/near complete clinical and radiological response (Complete Responders in the Breast – CRBr): A feasibility study
Presenter: Nisha Hariharan
Session: Poster display session
Resources:
Abstract
29P - Tumour response to neoadjuvant chemotherapy in breast cancer: Routine pathologic markers improve the predictive power of a cell-loss metric based on release of thymidine kinase 1 into blood
Presenter: Bernhard Tribukait
Session: Poster display session
Resources:
Abstract
30P - Comparison of metabolic changes between neoadjuvant chemotherapy and neoadjuvant endocrine therapy in premenopausal women with ER positive, HER2 negative breast cancer
Presenter: Ho-hyun Ryu
Session: Poster display session
Resources:
Abstract
31P - Circulating miR-155 as a potential therapeutic monitoring marker in breast cancer
Presenter: Sumadi Lukman Anwar
Session: Poster display session
Resources:
Abstract
32P - Profile of breast cancer epidemiology in Sanglah General Hospital, Denpasar, Bali from 2012 to 2019
Presenter: Citra Aryanti
Session: Poster display session
Resources:
Abstract
33P - Contrast enhanced chest CT in patients with breast cancer: Comprehensive imaging analysis and correlation with biological markers
Presenter: Bo Hwa Choi
Session: Poster display session
Resources:
Abstract
34P - Verification of metabolic regulatory mechanisms in androgen receptor-positive triple negative breast cancer
Presenter: Yuka Asano
Session: Poster display session
Resources:
Abstract
35TiP - Ribociclib plus goserelin with hormonal therapy versus physician choice chemotherapy in pre-/perimenopausal patients with HR+, HER2– inoperable locally advanced breast cancer (ABC): RIGHT choice study
Presenter: Yen-Shen Lu
Session: Poster display session
Resources:
Abstract
36TiP - A prospective study to assess response to neoadjuvant hormonal therapy in postmenopausal women with hormone-receptor positive breast cancer at a regional cancer centre in South India
Presenter: Shina Goyal
Session: Poster display session
Resources:
Abstract