<p>PVT1 Promotes the Proliferation and Migration of Non-Small Cell Lung Cancer via Regulating miR-148/RAB34 Signal Axis</p>

Abstract

It has been verified that long non-coding RNAs (lncRNAs) play critical roles in the development of human cancers. Increasing evidence indicates that lncRNA human plasmacytoma variant translocation1 (PVT1) was dysregulated in non-small cell lung cancer (NSCLC) which is the leading cause of cancer-related death. However, the precise mechanism underlying the effect of PVT1 remains elusive. Our research focused on the correlation of PVT1 to miR-148 and RAB34 in NSCLC. Methods: The quantitative real-time PCR (qRT-PCR) and western blot assay were used to detect gene and protein expression in NSCLC tissues and cells. CCK8, colony formation, transwell and wound healing assays were performed to evaluate the cell function of NSCLC cells. Dual-luciferase activity assay and RNA pull down assays were performed to verify the interaction between miR-148 and its targets. A xenograft test was conducted to detect the impact of RAB34 on tumor development in vitro. Results: In NSCLC tissues and cells, PVT1 and RAB34 were up-regulated, and miR-148 was down-regulated. Overexpression of PVT1 was capable of promoting NSCLC cell proliferation and migration which could be reversed by miR-148 restoration or RAB34 knock down. Also, our data firstly determined that the down-regulation of RAB34 had inhibitor effects while the up-regulation of RAB34 had promotive effects on tumor growth in vitro and in vivo. Conclusion: Those findings indicated that the signal pathway PVT1/miR-148/RAB34 play critical roles in the progression of NSCLC could be proposed in NSCLC as a possible diagnosis or therapeutic targets.

LncRNA PVT1 Is a Poor Prognosticator and Can Be Targeted by PVT1 Antisense Oligos in Gastric Adenocarcinoma

“…After about 10 days, tumors were formed in the back of all the mice, then the mice were randomly divided into three groups (control ASO, ASO#5, and ASO#6), and then mice were subcutaneously injected with control ASO or PVT1 ASO (50 mg/kg) three times a week for at least 3 weeks. Tumor size was measured with a digital caliper (VWR International) once tumors had reached a visible size, and tumor volume was determined by the formula: tumor volume (mm 3 ) = [length (mm) × width (mm) 2 ] × 0.52 [ 24 ].…”

“…Many studies have demonstrated that PVT1 is upregulated in a variety of human cancers, including GAC tissues and cell lines [ 17 , 18 ], non-small cell lung cancer [ 19 ], cervical cancer [ 20 ], and colorectal cancer [ 21 ], and serves as an onco-lncRNA in several tumor types [ 10 ]. Its aberrant expression can be a relatively independent regulatory factor for promoting tumorigenesis and MYC [ 22 , 23 , 24 ]. The upregulation of PVT1 suggests that it can be used for the early detection of cancer, the prognostication of drug resistance, or as a therapeutic target [ 25 , 26 ].…”

LncRNAs in Non-Small-Cell Lung Cancer

“…In addition to epigenetic silencing of LATS2, PVT1 also acts as a ceRNA for tumor suppressor miRNAs miR-200a and miR-200b to increase their target MMP-9, which promoted the invasive ability of NSCLC cells [78,80]. PVT1 also sponged miR-148 to increase Ras-related protein Rab-34 (RAB34), a GTPase that regulates surface proteins for invasion, to enhance the migration and invasion of NSCLC cells [81]. In a similar mechanism, XLOC-008466 and lncRNA 1308 increase MMP-2 and a disintegrin and metalloproteinase domain 15 (ADAM15) by competitively sponging miR-874 and miR-124, respectively, to increase the invasion of NSCLC cells [65,97].…”

Re-evaluating the need for mediastinal lymph node dissection and exploring lncRNAs as biomarkers of N2 metastasis in T1 lung adenocarcinoma

“…A previous study has shown that lncRNAs can modulate carcinogenesis and influence metastasis and invasion in various types of cancer (5). Consequently, several lncRNAs have the potential to be a biomarker for diagnosis, prognosis, and resistance for treatment in several cancers (6)(7)(8)(9)(10)(11)(12). LncRNAs may be effective biomarkers predicting N2 stage because of their expression specificity and powerful biological functions (13).…”