The functions of long noncoding RNAs on regulation of F-box proteins in tumorigenesis and progression

Abstract

Accumulated evidence has revealed that F-box protein, a subunit of SCF E3 ubiquitin ligase complexes, participates in carcinogenesis and tumor progression via targeting its substrates for ubiquitination and degradation. F-box proteins could be regulated by cellular signaling pathways and noncoding RNAs in tumorigenesis. Long noncoding RNA (lncRNA), one type of noncoding RNAs, has been identified to modulate the expression of F-box proteins and contribute to oncogenesis. In this review, we summarize the role and mechanisms of multiple lncRNAs in regulating F-box proteins in tumorigenesis, including lncRNAs SLC7A11-AS1, MT1JP, TUG1, FER1L4, TTN-AS1, CASC2, MALAT1, TINCR, PCGEM1, linc01436, linc00494, GATA6-AS1, and ODIR1. Moreover, we discuss that targeting these lncRNAs could be helpful for treating cancer via modulating F-box protein expression. We hope our review can stimulate the research on exploration of molecular insight into how F-box proteins are governed in carcinogenesis. Therefore, modulation of lncRNAs is a potential therapeutic strategy for cancer therapy via regulation of F-box proteins.

FBXL18 is required for ovarian cancer cell proliferation and migration through activating AKT signaling

“…In the SCF complex, FBPs recognize diverse substrates for ubiquitin ligation and subsequent degradation. Aberrations in the expression or activity of FBPs could contribute to the abnormal accumulation or degradation of their substrate proteins, and this process is usually involved in tumorigenesis [22][23][24]. FBXL8 loss excessively supported oncogene-induced transformation in vitro and lymphoma progression in vivo, which was mediated by polyubiquitylation of cyclin D3 and regulation of cyclin D3 protein stability [25].…”

Computational Ensemble Gene Co-Expression Networks for the Analysis of Cancer Biomarkers

“…The GATA6-AS1 lncRNA has been linked to the expression of F-box proteins [85], which play an important role in the degradation of key proteins in cellular regulation and tumorigenesis [86]. It has been studied in the context of lung, gastric, and ovarian cancer in association with the inhibition of signaling pathways and prevention of epithelialmesenchymal transition [87,88].…”

Prognostic significance of long noncoding RNA TTN‐AS1 in various malignancies

“…Titin‐antisense RNA1 (TTN‐AS1) is a newly identified lncRNA that maps to chromosome 2q31.2 7 . Clinically, there is evidence suggesting that overexpression of TTN‐AS1 strongly associates with poor prognosis in numerous malignancies, such as digestive system tumors, respiratory tumors, reproductive system cancers, breast cancer, and other malignancies 8 . Meanwhile, increased TTN‐AS1 expression is closely related to advanced tumor differentiation and tumor malignancy as well 7 .…”

“… 7 Clinically, there is evidence suggesting that overexpression of TTN‐AS1 strongly associates with poor prognosis in numerous malignancies, such as digestive system tumors, respiratory tumors, reproductive system cancers, breast cancer, and other malignancies. 8 Meanwhile, increased TTN‐AS1 expression is closely related to advanced tumor differentiation and tumor malignancy as well. 7 In glioblastomas, for example, decreasing the expression of TTN‐AS1 could remarkably prolong the survival of mice and reduce the volume of tumor through promoting apoptosis and inhibiting the migration, proliferation, and invasion of glioblastoma cells, which may be correlate with the reduction of binding between miR‐320b and transcriptional factor EGR3 mRNA.…”