ZEB1-activated LINC01123 accelerates the malignancy in lung adenocarcinoma through NOTCH signaling pathway

Abstract

Growing incidence of lung adenocarcinoma (LUAD) has been detected recently. Multiple long non-coding RNAs (lncRNAs) have been proven as tumor facilitators or inhibitors by extensive works. Present study concentrated on characterizing the potential role of LINC01123 in LUAD. We explored the differential expression of LINC01123 through qRT-PCR and found the amplification of LINC01123 in LUAD cell lines. It was ascertained that LINC01123 was definitely responsible for the malignant processes of LUAD cells. Further, we validated the ceRNA network of LINC01123/miR-449b-5p/NOTCH1 in LUAD via mechanical experiments. As a transcriptional factor related to epithelial mesenchymal transition (EMT), ZEB1 was responsible for the transcriptional activation of both LINC01123 and NOTCH1. The involvement of NOTCH signaling in LUAD was interrogated through evaluating functional changes after treating with FLI-06 (NOTCH pathway suppressor). It showed that FLI-06-caused NOTCH signaling inactivation suppressed malignant functions in LUAD cells. Additionally, LINC01123 facilitated NOTCH1-dependent NOTCH signaling activation. Rescue experiments probed the modulatory function of LINC01123/miR-449b-5p/NOTCH1 in LUAD cellular processes. Altogether, ZEB1-activated LINC01123 accelerates the malignancy in LUAD through miR-449b-5p/NOTCH1 axis-mediated NOTCH signaling pathway, while NOTCH1 boosts ZEB1 in return. These observations suggest the huge potential of LINC01123 as a new target for LUAD therapy.

Characterizing the Copy Number Variation of Non-Coding RNAs Reveals Potential Therapeutic Targets and Prognostic Markers of LUSC

“…Similarly, the lncRNA LINC01133 may regulate the activity of tumor suppressor pathways by dysregulating ACTL6A , SMARCD2 , SMO , PHC3 , and CENPP ( Figure 6B,D ). It is worth noting that LINC01133 has been shown to be closely related to the invasion and malignant proliferation of human non-small cell lung cancer ( Zhang et al, 2020 ; Geng et al, 2021 ). The lncRNA LINC00896 is associated with copy number variation syndrome by regulating the corresponding target gene ( Supplementary Figure S2B ).…”

Low PRRX1 expression and high ZEB1 expression are significantly correlated with epithelial-mesenchymal transition and tumor angiogenesis in non-small cell lung cancer

“…[ 33 – 36 ] In previous reports, some factors affected NSCLC tumor development and progression by the regulation of ZEB1. [ 37 , 38 ] Nevertheless, the mechanism of ZEB1 as an activator remains unclear. In this study, ZEB1+ expression was higher in the NSCLC group than in the control group, and it was positively associated with tumor size, LNM, DM, and TNM stage.…”

Long non‑coding RNA MIR4713HG aggravates malignant behaviors in oral tongue squamous cell carcinoma via binding with microRNA let‑7c‑5p

“…Long non-coding RNAs and microRNAs are two subtypes of non-coding RNAs with different lengths. It has been well documented that lncRNAs can act as endogenous competing RNAs that interact with miRNAs and participate in human diseases, such as cancer ( 32 , 33 ). In OTSCC, the potential regulating role of lncRNAs remains unclear, except for one lncRNA, HOTTIP, which has been reported to act as an oncogenic factor in OTSCC ( 17 ).…”