KLF5-induced BBOX1-AS1 contributes to cell malignant phenotypes in non-small cell lung cancer via sponging miR-27a-5p to up-regulate MELK and activate FAK signaling pathway

Abstract

Background Non-small cell lung cancer (NSCLC) is a major histological subtype of lung cancer with high mortality and morbidity. A substantial amount of evidence demonstrates long non-coding RNAs (lncRNA) as critical regulators in tumorigeneis and malignant progression of human cancers. The oncogenic role of BBOX1 anti-sense RNA 1 (BBOX1-AS1) has been reported in several tumors. As yet, the potential functions and mechanisms of BBOX1-AS1 in NSCLC are obscure. Methods The gene and protein expression was detected by qRT-PCR and western blot. Cell function was determined by CCK-8, colony forming, would healing and transwell assays. Bioinformatics tools, ChIP assays, dual luciferase reporters system and RNA pull-down experiments were used to examine the interaction between molecules. Subcutaneous tumor models in nude mice were established to investigate in vivo NSCLC cell behavior. Results BBOX1-AS1 was highly expressed in NSCLC tissues and cells. High BBOX1-AS1 expression was associated with worse clinical parameters and poor prognosis. BBOX1-AS1 up-regulation was induced by transcription factor KLF5. BBOX1-AS1 deficiency resulted in an inhibition of cell proliferation, migration, invasion and EMT in vitro. Also, knockdown of BBOX1-AS1 suppressed NSCLC xenograft tumor growth in mice in vivo. Mechanistically, BBOX1-AS1 acted act as a competetive “sponge” of miR-27a-5p to promote maternal embryonic leucine zipper kinase (MELK) expression and activate FAK signaling. miR-27a-5p was confirmed as a tumor suppressor in NSCLC. Moreover, BBOX1-AS1-induced increase of cell proliferation, migration, invasion and EMT was greatly reversed due to the overexpression of miR-27a-5p. In addition, the suppressive effect of NSCLC progression owing to BBOX1-AS1 depletion was abated by the up-regulation of MELK. Consistently, BBOX1-AS1-mediated carcinogenicity was attenuated in NSCLC after treatment with a specific MELK inhibitor OTSSP167. Conclusions KLF5-induced BBOX1-AS1 exerts tumor-promotive roles in NSCLC via sponging miR-27a-5p to activate MELK/FAK signaling, providing the possibility of employing BBOX1-AS1 as a therapeutic target for NSCLC patients.

Long non-coding RNA BBOX1-antisense RNA 1 enhances cell proliferation and migration and suppresses apoptosis in oral squamous cell carcinoma via the miR-3940-3p/laminin subunit gamma 2 axis

“…LncRNA gamma-butyrobetaine hydroxylase 1 (BBOX1)-antisense RNA 1 (AS1) exists as an oncogene in most tumor cells. Abnormally high expression levels of BBOX1-AS1 are observed in most cancers, such as lung [ 7 ], cervical [ 8 ], and esophageal cancers [ 9 ], and BBOX1-AS1 is strongly linked to the overall survival of patients with these cancers, which suggests that targeting BBOX1-AS1 may be used as a therapeutic approach for cancer treatment. However, the regulatory effects of BBOX1-AS1 on OSCC development have not yet been elucidated.…”

LncRNA BBOX1-AS1 promotes pituitary adenoma progression via sponging miR-361-3p/E2F1 axis

“…Many current research work have revealed that the interaction between lncRNA and specific miRNA can regulate cancer progression [7,10,13]. Furthermore, since miRNA is absorbed by lncRNA and targets mRNA, it is thought to be a significant regulator in biologic processes [25].…”

“…However, the specific role of BBOX1-AS1 in pituitary adenoma is still rarely reported. Many current research works have revealed that the interaction between specific miRNA and lncRNA can regulate cancer progression [7,10,13]. Previous studies showed that BBOX1-AS1 sponging miR-361-3p results in abrogation of the antitumorigenic potential of miR-361-3p in different cancers.…”

Multiomics Differences in Lung Squamous Cell Carcinoma Patients with High Radiosensitivity Index Compared with Those with Low Radiosensitivity Index

“…Compared with the LRSI group, KLF5 was the most significant gene for CNV in the HRSI group. KLF5 plays an important role in the DNA damage response by regulating DNA damage checkpoint proteins and is associated with cisplatin DDP resistance [ 33 – 35 ]. The relationship between KLF5 and radiotherapy sensitivity needs to be discovered.…”