Long non‑coding RNA DANCR represses the viability, migration and invasion of multiple myeloma cells by sponging miR‑135b‑5p to target KLF9

Abstract

Multiple myeloma (MM) is a malignancy of plasma cells that leads to marrow failure and bone lesions. Numerous studies have verified the link between long non-coding RNAs (lncRNAs) and MM. The present study aimed to examine the role and underlying mechanism of differentiation antagonizing non-protein coding RNA (DANCR) in MM cells. The relative expression levels of DANCR, microRNA (miR)-135b-5p and Krüppel-like factor 9 (KLF9) were examined using reverse transcription-quantitative PCR. Cell viability was assessed using the MTT assay, while relative cell migration and invasion were evaluated using Transwell assays. Moreover, the dual-luciferase reporter assay was used to examine the interplay between DANCR, miR-135b-5p and KLF9. Western blotting was performed to determine the expression level of KLF9. It was found that lncRNA DANCR and KLF9 were downregulated, while miR-135b-5p was upregulated in the serum of patients with MM and in MM cells compared with the controls. Overexpressing DANCR or knocking down miR-135b-5p reduced the viability of the MM cells, as well as restrained MM cells from migrating and invading. Furthermore, DANCR directly targeted miR-135b-5p and was negatively correlated with miR-135b-5p. It was also found that KLF9 was targeted by miR-135b-5p and was inversely correlated with miR-135b-5p expression. The impact of lncRNA DANCR-mediated suppression on cell viability, invasion and migration was partially abolished by short hairpin RNA KLF9 or miR-135b-5p mimics transfection in MM cells. Thus, it was suggested that lncRNA DANCR repressed the viability, migration and invasion of MM cells by sponging miR-135b-5p to target KLF9.

Krüppel-like Factor-9 and Krüppel-like Factor-13: Highly Related, Multi-Functional, Transcriptional Repressors and Activators of Oncogenesis

“…Cervical cancer patients exhibit lower blood levels of KLF9 mRNA compared to healthy non-cancerous controls, suggesting the possible utility of KLF9 as a non-invasive biomarker for this cancer type [164]. However, similar findings have been limited for other cancers, with the exception of multiple melanoma [165]. In contrast, KLF13 is over-expressed in cervical cancer cell lines, and KLF13 expression in normal cervical epithelium is low but increases in intraepithelial cervical neoplasia and invasive squamous cervical cancer.…”

“…KLF9 mRNA levels in the sera of multiple myeloma (MM) patients are significantly lower than that for healthy subjects [165]. miR-135b-5p directly targets KLF9 mRNA in MM cells, and the consequent repression of KLF9 expression favors increased proliferation and invasion in vitro [165].…”

“…KLF9 mRNA levels in the sera of multiple myeloma (MM) patients are significantly lower than that for healthy subjects [165]. miR-135b-5p directly targets KLF9 mRNA in MM cells, and the consequent repression of KLF9 expression favors increased proliferation and invasion in vitro [165]. KLF9 is a mediator of drug-induced apoptosis in MM plasma cells and its levels are induced in these cells by bortezomib in combination with an HDAC inhibitor [150].…”

Krüppel-like factors in tumors: Key regulators and therapeutic avenues

“…Among lncRNAs, differentiation antagonizing non-protein coding RNA (DANCR) showed the most extensive regulation with KLFs. DANCR exhibits different biological functions in different tumor types: KLF12 mediates the promotive effect of DANCR in HCC ( 218 ), while KLF9 is the ultimate target of the cancer-inhibiting effect of DANCR in multiple myeloma ( 219 ). By upregulating anticancer KLFs or knocking down KLFs that mediate carcinogenesis, clinicians can mitigate the detrimental effects of lncRNA maladjustment on tumorigenesis.…”

Long non‑coding RNAs in multiple myeloma (Review)

“…The OIP5-AS1/miR-27a-3p/tuberous sclerosis 1 pathway inhibits tumor cell migration and invasion and promotes apoptosis (70). Differentiation antagonizing non-protein coding RNA (DANCR) forms the DANCR/miR-135b-5p/KLF9 pathway, which reduces tumor cell viability, migration and invasion (71). Insulin-like growth factor receptor antisense imprinted non-protein coding RNA (IRAIN) forms the IRAIN/miR-125b pathway to inhibit tumor cell proliferation and promote apoptosis (72).…”