Long non-coding RNA OIP5-AS1 suppresses multiple myeloma progression by sponging miR-27a-3p to activate TSC1 expression

Abstract

Background: Multiple myeloma (MM) is a prevalent hematological malignancy. Long noncoding RNAs are correlated with the development of MM. In this project, the function of lncRNA opa interacting protein 5-antisense 1 (OIP5-AS1) in MM and the potential mechanistic pathway were explored. Methods: The expression of OIP5-AS1, microRNA (miR)-27a-3p and tuberous sclerosis 1 (TSC1) was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay and Bromodeoxyuridine (BrdU) staining. And cell apoptosis was evaluated by flow cytometry assay. Cell metastasis was assessed utilizing transwell assay. Western blot analysis was employed to detect protein level. The target relation between miR-27a-3p and OIP5-AS1 or TSC1 was confirmed via dual-luciferase reporter assay and RNA immunoprecipitation assay. Tumor xenograft assay was conducted to measure the function of OIP5-AS1 in vivo. Results: The expression levels of OIP5-AS1 and TSC1 were decreased in MM, whereas miR-27a-3p was upregulated. High level of OIP5-AS1 could predict favourable prognosis of MM patients. Overexpression of OIP5-AS1 inhibited cell viability, colony formation ability, migration and invasion, induced cell cycle arrest in G1 phase and apoptosis of MM cells in vitro as well as repressed tumorigenesis in vivo. MiR-27a-3p was a target of OIP5-AS1, and reversed the impact of OIP5-AS1 on MM cells. MiR-27a-3p directly targeted TSC1. Silencing of miR-27a-3p repressed MM progression by elevating TSC1 expression. OIP5-AS1 upregulated TSC1 by sponging miR-27a-3p. Conclusion: OIP5-AS1 repressed multiple myeloma progression by regulating miR-27a-3p/TSC1 axis.

The Role of lncRNAs in the Pathobiology and Clinical Behavior of Multiple Myeloma

“…Moreover, the knockdown of LINC01234 increases miR-124-3p and suppresses GRB2 expression, resulting in a decrease of cell proliferation and the inhibition of MM growth. These results demonstrate that lncRNAs play an important role in the pathobiology of MM ( Table 1 ) [ 13 , 33 , 34 , 35 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 48 , 50 , 51 , 53 , 56 , 57 , 58 , 59 , 62 , 69 , 72 , 78 , 79 , 81 , 82 , 83 , 84 , 85 , 86 , 88 , 90 , 91 , 92 , 94 , 95 , 96 , 97 , 107 ].…”

“…However, an increasing number of studies in MM are showing that lncRNAs can regulate or can be regulated by more than one miRNA, such as H19 (H19 imprinted maternally expressed transcript), UCA1 (urothelial cancer associated 1) or OIP5-AS1 (OIP5 antisense RNA 1). Remarkably, there are cases like TUG1 (taurine up-regulated 1) and H19 that are associated with the regulation of the same miRNA, miR-29b-3p ( Table 1 ) [ 33 , 39 , 42 , 44 , 45 , 51 , 53 , 57 , 58 , 59 , 60 , 72 , 81 , 82 , 83 , 88 , 90 , 91 , 94 , 95 , 96 ]. These results highlight the relevance of the miRNA sponge function of lncRNAs in MM.…”

LncRNA OIP5-AS1 Affects the Malignant Biological Behavior of Ovarian Cancer via the miR-153-3p/KLF5 Axis

“…The knockdown of OIP5-AS1 inhibited the proliferation, invasion and migration of ovarian cancer cells, and promoted the apoptosis of ovarian cancer cells to a certain extent. OIP5-AS1 has been identi ed as an oncogene of human diseases in a variety of cancer cells, such as breast cancer cells [30] , non-small cell lung cancer cells [5] , pancreatic ductal carcinoma cells [29] , and multiple myeloma cells [28] .…”

“…Moreover, lncRNAs play their roles through a variety of complex molecular mechanisms [20] , such as affecting the epigenetic activity of tumor cells in the nucleus, gene transcription and post-transcriptional modi cation of mRNA [2] . LncRNA OIP5-AS1 has been reported to inhibit the proliferation of multiple malignant tumors [29,28] . It can regulate a variety of biological activities of cells in some diseases and tumors.…”

The role of EMT-related lncRNA in the process of triple-negative breast cancer metastasis

“…Linc-OIP5, a novel linc-Opa interacting protein 5, has found to be dysregulated in many malignant tumors [ 41 , 42 ]. For example, Linc-OIP5 as an oncogene promotes biological behaviors such as proliferation, migration, and invasion in lung adenocarcinoma and multiple myeloma.…”