LncRNA ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of lung adenocarcinoma

Abstract

Background Growing evidence suggests that suppressor of tumorigenicity 7 antisense RNA 1 (ST7-AS1) is an oncogenic long noncoding RNA (lncRNA). However, little is known on its clinical significance, biological functions, or molecular mechanisms in lung adenocarcinoma (LUAD). Methods The expression of ST7-AS1 and miR-181b-5p were examined by qRT-PCR. The correlations between ST7-AS1 level and different clinicopathological features were analysed. In vitro, LUAD cells were examined for cell viability, migration and invasion by MTT, wound healing and Transwell assay, respectively. Epithelial-mesenchymal transition (EMT) biomarkers were detected by Western blot. The regulations between ST7-AS1, miR-181b-5p, and KPNA4 were examined by luciferase assay, RNA immunoprecipitation, RNA pulldown. Both gain- and loss-of-function strategies were used to assess the importance of different signalling molecules in malignant phenotypes of LUAD cells. The in vivo effect was analysed using the xenograft and the experimental metastasis mouse models. Results ST7-AS1 was upregulated in LUAD tissues or cell lines, correlated with tumours of positive lymph node metastasis or higher TNM stages, and associated with shorter overall survival of LUAD patients. ST7-AS1 essentially maintained the viability, migration, invasion, and EMT of LUAD cells. The oncogenic activities of ST7-AS1 were accomplished by sponging miR-181b-5p and releasing the suppression of the latter on KPNA4. In LUAD tissues, ST7-AS1 level positively correlated with that of KPNA4 and negatively with miR-181b-5p level. In vivo, targeting ST7-AS1 significantly inhibited xenograft growth and metastasis. Conclusions ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of LUAD cells. Targeting ST7-AS1 and KPNA4 or up-regulating miR-181b-5p, therefore, may benefit the treatment of LUAD.

LncRNA TUG1/miR-29c-3p/SIRT1 axis regulates endoplasmic reticulum stress-mediated renal epithelial cells injury in diabetic nephropathy model in vitro

“…On the other hand, TUG1 also decreased the luciferase activity in miR-29c-3p-WT-expressing cells, but not in mutant miR-29c-3p-expressing cells ( Fig 3B ). Furthermore, RIP assay revealed the presence of both TUG1 and miR-29c-3p in the same complex as Ago2, the catalytic component in the RNA-induced silencing complex[ 25 ] ( S3B Fig ). Then miR-29c-3p was predicted to interact with SIRT1 ( Fig 3C ).…”

Autophagy related long non-coding RNA and breast cancer prognosis analysis and prognostic risk model establishment

“…Studies have shown that the role of ST7-AS1 in tumors is mainly to promote tumor progression. The lncRNA ST7-AS1 promotes malignancy in lung adenocarcinoma by regulating the miR-181b-5p/KPNA4 axis (24). The lncRNA ST7-AS1 promotes TRPM7 expression by upregulating microRNA-543 thereby promoting cervical cancer progression (25).…”

Comprehensive analysis of karyopherin alpha family expression in lung adenocarcinoma: Association with prognostic value and immune homeostasis

“…KPNA7 promotes cell growth and anchorage-independent growth, and reduces autophagy of pancreatic cancer cells ( Laurila et al, 2014 ). Previous studies have reported overexpression of KPNA4 in LUAD and identified it as a potential key driver of the malignant phenotype ( Hu et al, 2020 ). Nonetheless, the functional role and underlying mechanism of the KPNA family in LUAD are poorly understood.…”