Identification of four potential predicting miRNA biomarkers for multiple myeloma from published datasets.
BACKGROUND
Multiple myeloma is a cancer which has a high occurrence rate and causes great injury to people worldwide. In recent years, many studies reported the effects of miRNA on the appearance of multiple myeloma. However, due to the differences of samples and sequencing platforms, a large number of inconsistent results have been generated among these studies, which limited the cure of multiple myeloma at the miRNA level.


METHODS
We performed meta-analyses to identify the key miRNA biomarkers which could be applied on the treatment of multiple myeloma. The key miRNAs were determined by overlap comparisons of seven datasets in multiple myeloma. Then, the target genes for key miRNAs were predicted by the software TargetScan. Additionally, functional enrichments and binding TFs were investigated by DAVID database and Tfacts database, respectively.


RESULTS
Firstly, comparing the normal tissues, 13 miRNAs were differently expressed miRNAs (DEMs) for at least three datasets. They were considered as key miRNAs, with 12 up-regulated (hsa-miR-106b, hsa-miR-125b, hsa-miR-130b, hsa-miR-138, hsa-miR-15b, hsa-miR-181a, hsa-miR-183, hsa-miR-191, hsa-miR-19a, hsa-miR-20a, hsa-miR-221 and hsa-miR-25) and one down-regulated (hsa-miR-223). Secondly, functional enrichment analyses indicated that target genes of the upregulated miRNAs were mainly transcript factors and enriched in transcription regulation. Besides, these genes were enriched in multiple pathways: the cancer signal pathway, insulin signal metabolic pathway, cell binding molecules, melanin generation, long-term regression and P53 signaling pathway. However, no significant enrichment was found for target genes of the down-regulated genes. Due to the distinct regulation function, four miRNAs (hsa-miR-19a has-miR-221 has-miR25 and has-miR223) were ascertained as the potential prognostic and diagnostic markers in MM. Thirdly, transcript factors analysis unveiled that there were 148 TFs and 60 TFs which bind target genes of the up-regulated miRNAs and target genes of the down-regulated miRNAs, respectively. They respectively generated 652 and 139 reactions of TFs and target genes. Additionally, 50 (31.6%) TFs were shared, while higher specificity was found in TFs of target genes for the upregulated miRNAs.


CONCLUSIONS
Together, our findings provided the key miRNAs which affected occurrence of multiple myeloma and regulation function of these miRNAs. It is valuable for the prognosis and diagnosis of multiple myeloma.
Department of Clinical Laboratory Center, Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, China.
Tian
T
Xiang
The Department of Orthopedic Surgery, People's Hospital of Three Gorges University, YiChang, Hubei, China.
Ai-Xin
AX
Hu
Department of Orthopedics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.
Peng
P
Sun
Department of Gastrointestinal Surgery, Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, China.
Gao
G
Liu
Department of Orthopedics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China.
Gang
G
Liu
Department of Hematology, The Affiliated Huai'an Hospital of Xuzhou Medical College and The Second People's Hospital of Huai'an, Huai'an, China.
Yan
Y
Xiao
Enrichment analysis; Mirna; Multiple myeloma; Signature