Long non coding RNA OIP5‑AS1 promotes metastasis of breast cancer via miR‑340‑5p/ZEB2 axis

Abstract

Breast cancer is the most common invasive cancer in women with the highest number of related deaths which is caused by distal metastasis. Recently, integrated analysis of gene expression profile suggested widespread gene dysregulation in various types of cancer. Research in the past decade has focused on long non-coding RNAs (lncRNAs), particularly in cell proliferation, tumor progression and metastasis. OPA-interacting protein 5 antisense transcript 1 (OIP5-AS1) is an evolutionarily conserved long non-coding RNA that has been linked to oncogenesis in multiple cancers. In breast cancer, dysregulation of OIP5-AS1 was reported but the precise role in cancer development and progression remains unclear. In the present study, using small interfering RNA (siRNA) targeting OIP5-AS1, it was shown that knockdown of OIP5-AS1 was associated with alteration of EMT markers and suppressed migration and invasion of breast cancer cells. Among the EMT-related transcription factors, ZEB1 and ZEB2 were significantly downregulated with OIP5-AS1 knockdown. Computational analysis and a dual-luciferase reporter system identified miR-340-5p was the target gene for OIP5-AS1. Further experiments verified the function of OIP5-AS1 in cell invasion was dependent on miR-340a-5p through regulating target gene ZEB2. In vivo study demonstrated that overexpressing OIP5-AS1 in breast cancer cells promoted lung metastasis in nude mice. The findings of the present study revealed the mechanism of OIP5-AS1 in breast cancer metastasis. Overall, our study may provide a potential therapeutic target for breast cancer metastasis.

Long intergenic non-protein coding RNA 1094 (LINC01094) promotes the progression of breast cancer (BC) by regulating the microRNA-340-5p (miR-340-5p)/E2F transcription factor 3 (E2F3) axis

“…As the targeted miRNA of LINC00662, miR-340-5p expression is reduced in colonic carcinoma tissues, and the inhibition of miR-340-5p expression promotes colonic carcinoma cell proliferation, migration, and invasion, and restrains apoptosis [ 32 , 33 ]. In BC tissues, miR-340-5p expression is reduced, which is closely associated with the clinicopathological indicators of patients, and inhibiting miR-340-5p expression helps stabilize ZEB2 protein level and promote the metastasis of BC cells [ 34 ]. In this study, bioinformatics analysis predicted a binding site between LINC01094 and miR-340-5p, and this prediction was validated by dual-luciferase reporter gene and RIP assays.…”

Identification and Roles of miR-29b-1-3p and miR29a-3p-Regulated and Non-Regulated lncRNAs in Endocrine-Sensitive and Resistant Breast Cancer Cells

“…OIP5-AS triggers target-directed miRNA degradation (TDMD) of miR-7 in human cell line K562 [ 85 ]. Other studies have demonstrated that OIP5-AS 1 acts as a ceRNA for miR-340-5p, which normally targets and downregulates ZEB2 [ 86 ] and for miR-216a-5p [ 87 ] in BC cells. The reduction of OIP5-AS1 abundance by miR-29a-3p and miR-29b-1-3p fits with their ‘anti-tumorigenic’ activity in BC (reviewed in [ 30 ]).…”

SUMOylation of IGF2BP2 Promotes Vasculogenic Mimicry of Glioma Via Regulating OIP5-AS1/miR-495-3p

“…It plays an essential role in regulating tumorigenesis and development of the tumors (26). Current study has shown that OIP5-AS1was up-regulated in breast cancer which regulates the expression of ZEB2 by acting as competitive endogenous RNA (ceRNA) for miR-340-5p, and then promotes metastasis of breast cancer (27). Similarly, OIP5-AS1 regulated ovarian cancer progression via miR-137/ZNF217 axis (28).…”