Long noncoding RNA LINC00520 prevents the progression of cutaneous squamous cell carcinoma through the inactivation of the PI3K/Akt signaling pathway by downregulating EGFR

Abstract

Background: Long noncoding RNAs (lncRNAs) play pivotal roles in various malignant tumors. Epidermal growth factor receptor (EGFR) signaling is associated with the pathogenesis of cutaneous squamous cell carcinoma (cSCC). This study aimed to explore the role of LINC00520 in the development of cSCC via EGFR and phosphoinositide 3-kinase-protein kinase B (PI3K/Akt) signaling pathways. Methods: A microarray analysis was applied to screen differentially expressed lncRNAs in cSCC samples. The A431 cSCC cell line was transfected and assigned different groups. The expression patterns of LINC00520, EGFR, and intermediates in the PI3K/Akt pathway were characterized using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting analysis. Cell proliferation, migration, and invasion were detected using the MTT assay, scratch test, and Transwell assay, respectively. Cell-based experiments and a tumorigenicity assay were conducted to assess the effect of LINC00520 on cSCC progression. This study was ended in September 2017. Comparisons between two groups were analyzed with t -test and comparisons among multiple groups were analyzed using one-way analysis of variance. The nonparametric Wilcoxon rank sum test was used to analyze skewed data. The enumerated data were analyzed using the chi-square test or Fisher exact test. Results: Data from chip GSE66359 revealed depletion of LINC00520 in cSCC. Cells transfected with LINC00520 vector and LINC00520 vector + si-EGFR showed elevated LINC00520 level but decreased levels of the EGFR, PI3K, AKT, VEGF, MMP-2 and MMP-9 mRNAs and proteins, and inhibition of the growth, migration and adhesion of cSCC cells, while the si-LINC00520 group showed opposite trends (all P < 0.05). Compared with the LINC00520 vector group, the LINC00520 vector + si- EGFR group showed decreased levels of the EGFR, PI3K, AKT, VEGF, MMP-2 and MMP-9 mRNAs and proteins, and inhibition of the growth, migration and adhesion of cSCC cells, while the LINC00520 vector + EGFR vector group showed opposite results (all P < 0.05). Conclusion: Based on our results, LINC00520-targeted EGFR inhibition might result in the inactivation of the PI3K/Akt pathway, thus inhibiting cSCC development.

Long non-coding RNA LINC00520 promotes the proliferation and metastasis of malignant melanoma by inducing the miR-125b-5p/EIF5A2 axis

“…Long intergenic non-protein coding RNA 520 (LINC00520), located on chromosome 14, has been reported to overexpress and function as a oncogene in breast cancer, nasopharyngeal carcinoma and laryngeal squamous cell carcinoma [12][13][14]. It has also been showed that LINC00520 inhibits the growth and metastasis of cutaneous squamous cell carcinoma [15]. However, the exact role and molecular mechanism of LINC00520 in malignant melanoma has not been studied.…”

Topoisomerase II alpha promotes gallbladder cancer proliferation and metastasis through activating phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway

“…[ 22 ] PI3K and Akt are the main proteins involved in this signaling pathway, and this pathway is stimulated by assorted oncogenes and growth factor receptors. [ 23 , 24 ] PI3K/Akt/mTOR pathway has been reported to be associated with GBC progression, [ 16 – 18 ] however to the best of our knowledge, there is no study about the relationship between TOP2A and GBC or TOP2A and PI3K/Akt/mTOR pathway. Hence, in our study, we explored the association between GBC, TOP2A, and PI3K/Akt/mTOR pathway.…”

Long non-coding RNAs in cutaneous biology and keratinocyte carcinomas

“…Downregulation of LINC00520 has been noted in A431 cSCC cell line, compared to NHEKs, and overexpression of LINC00520 in A431 cells results in suppression of tumor growth and lymph node metastasis [123]. A431 cells express high levels of EGFR [124].…”