The long non-coding RNA PVT1/miR-145-5p/ITGB8 axis regulates cell proliferation, apoptosis, migration and invasion in non-small cell lung cancer cells

Abstract

Lung cancer is one of the leading causes of death worldwide and non-small cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer. Long noncoding RNAs (lncRNAs) are closely associated with the development and progression of various cancers, including lung cancer. The purpose of this study was to explore the potential role and molecular mechanism of lncRNA plasmacytoma variant translocation 1 (PVT1) in regulating the proliferation, apoptosis, migration, and invasion of NSCLC cells. The expressions of PVT1, integrin β-8 (ITGB8), and miR-145-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of ITGB8, MEK, p-MEK, ERK, and p-ERK were measured by western blot analysis. Cell proliferation, apoptosis, migration, and invasion were determined by MTT assay, flow cytometry, and transwell assay, respectively. The potential binding sites between miR-145-5p and PVT1 or ITGB8 were predicted by online software and verified by luciferase reporter assay. A xenograft tumor model was established to confirm the effect of PVT1 on NSCLC in vivo. We found out that the expression levels of PVT1 and ITGB8 were upregulated in NSCLC tissues and cells. Knockdown of PVT1 or ITGB8 suppressed cell proliferation, migration, invasion and promoted apoptosis in NSCLC cells, which could be reversed by ITGB8 overexpression in NSCLC cells. Moreover, PVT1 could regulate ITGB8 expression via direct binding to miR-145-5p. Furthermore, PVT1 regulated the MEK/ERK pathway by affecting ITGB8 expression. In addition, knockdown of PVT1 inhibited tumor growth, ITGB8 expression, MEK/ERK signaling pathway, and increased miR-145-5p expression in vivo. In conclusion, the knockdown of PVT1 inhibited proliferation, migration, and invasion but induced apoptosis of NSCLC cells by regulating miR-145-5p/ITGB8 axis and inhibiting MEK/ERK signaling pathway, providing a novel avenue for the treatment of NSCLC.

Hsa_circ_0016760 exacerbates the malignant development of non‑small cell lung cancer by sponging miR‑145‑5p/FGF5

“…According to existing literature, miR-145-5p in NSCLC has been reported to be regulated by multiple long-chain non-coding RNAs, including SNHG1, JPX and PVT1. These long-chain non-coding RNAs have been revealed to exhibit cancer-promoting effects in NSCLC by enhancing the expression of downstream coding genes via sponging miR-145-5p (19)(20)(21). At present, studies on whether miR-145-5p is regulated by circRNAs in NSCLC are scarce.…”

Single-cell Transcriptomic Analysis of Eutopic Endometrium and Ectopic Lesions of Adenomyosis

“…The DEGs (p value < 0.05, fold change > 1.5) in AM_EC versus AM_EM are presented as volcano maps, and analysis of the upregulated genes with log 2 fold change > 1 showed that the functions of a series of genes were related to angiogenesis (such as MMP1 and ESM1), in ammation (such as CXCL8 [26]) and cell motility (such as ITGA2 [27] and ITGB8 [28]) (Fig. 3D).…”

LncRNAs in Non-Small-Cell Lung Cancer

“…PRKCZ antisense RNA 1 (PRKCZ-AS1) led to enhanced mitogen-activated protein kinase (MAPK) signaling by inhibiting mir-766-5p and increasing its target MAPK1 to enhance NSCLC proliferation and migration [76]. PVT1 can also regulate activation of MAPK signaling by sponging miR-145-5p and increasing integrin subunit beta 8 (ITGB8), as well as activate the wingless (Wnt)/β-catenin pathway by sponging mir-361 and increasing SRY-box transcription factor 9 (SOX9) for enhanced NSCLC tumorigenesis [82,83]. As discussed previously, PVT1 was shown to have roles in cell-cycle regulation and the regulation of proteins for invasion and migration and, therefore, be a promising therapeutic target due to its multiple functions in NSCLC progression.…”