Long non-coding RNA PVT1 promotes osteosarcoma development by acting as a molecular sponge to regulate miR-195

Abstract

A growing body of evidence has indicated that long non-coding RNAs (lncRNAs) serve as competing endogenous RNAs (ceRNAs) during oncogenesis. In this study, the qRT-PCR results indicated that the lncRNA PVT1 is overexpressed in osteosarcoma and decreased the survival rate of osteosarcoma patients. MTT and clonal colony formation assays were used to detect the effect of PVT1 on proliferation, and flow cytometry was performed to assess apoptosis and the cell cycle. A Transwell assay was used to analyze migration and invasion. The results revealed that silencing PVT1 by siRNA inhibited proliferation, migration and invasion and promoted apoptosis and cell cycle arrest in osteosarcoma cells. Furthermore, a gene microarray was used to screen differentially expressed miRNAs associated with PVT1. The interaction between PVT1 and miRNAs was then analyzed by qRT-PCR and luciferase reporter gene assay. We found that PVT1 negatively regulated miR-195 in osteosarcoma cells. Simultaneously, we found that silencing PVT1 by siRNA suppressed proliferation, migration and invasion and promoted cell cycle arrest and apoptosis via miR-195 in osteosarcoma cells. Moreover, silencing PVT1 by siRNA inhibited BCL2, CCND1, and FASN protein expression via miR-195 in osteosarcoma cells, and BCL2 inhibited the si-PVT1#1-induced apoptosis of U2OS cells. CCND1 inhibited the cell cycle arrest of U2OS cells induced by si-PVT1#1. FASN promoted the invasiveness U2OS cells, which was inhibited by si-PVT1#1. Therefore, our study demonstrated that PVT1 may be a therapeutic target for treatment of osteosarcoma.

Knockdown of Lncrna PVT1 Enhances Radiosensitivity in Non-Small Cell Lung Cancer by Sponging Mir-195

“…Also, tumor xenografts experiments suggested that PVT1 knockdown sensitized NSCLC cells to radiotherapy in vivo , which was significantly relieved by miR-195 inhibitor. In line with our study, PVT1 was demonstrated to act as a molecular sponge of miR-195 to promote osteosarcoma development [36]. …”

Overexpression of LncRNA PVT1 Predicts Advanced Clinicopathological Features and Serves as an Unfavorable Risk Factor for Survival of Patients with Gastrointestinal Cancers

“…Plasmacytoma variant translocation 1 (PVT1) has been a rising star among lncRNAs, it was transcribed by the human PVT1 gene located in chromosomal 8q24.21[14, 15]. LncRNA PVT1 was reported to play an important role in various cancers [16-18] and function as an oncogene in the development of tumors through promoting cell proliferation, inhibiting cell apoptosis and enhancing cell migration [16-19]. …”

Prognostic value of abnormally expressed long non-coding RNAs in patients with osteosarcoma: a meta-analysis

“…Of these, 129 duplicated articles were excluded; through title and abstract review, studies describing unrelated topics (n = 80) which refers to those studies that were not research articles or those studies unrelated to osteosarcoma, lncRNA , or patient prognosis were removed; after reading the remaining 54 full-text articles, studies lacking relevant data (n = 32), studies presented in language other than English (n = 1), fulltext unavailable studies (n = 1), and the studies of which included patients were reported in previous studies (n = 1) were excluded. Eventually, 19 studies (containing 1298 patients) met the inclusion criteria and were evaluated in this analysis [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]. The screening process and results was shown in Figure 1.…”