Hypoxia-induced PVT1 promotes lung cancer chemoresistance to cisplatin by autophagy via PVT1/miR-140-3p/ATG5 axis

Abstract

Lung cancer is one of the most common and lethal malignant tumors and the cases increased rapidly. Elevated chemoresistance during chemotherapy resistance remains a challenge. Hypoxia is one of the components that lead to chemoresistance. PVT1 participates in various tumor drug resistance and is associated with hypoxia conditions. The present study aimed to analyze the regulatory relationship of hypoxia and PVT1 and the mechanism of PVT1 in the hypoxia-induced chemoresistance process of lung cancer. The expression of PVT1 in lung cancer and adjacent tissues, and cell lines were analyzed using the TCGA database and qPCR. The regulatory relationship between hypoxia and PVT1 was validated and analyzed with qPCR, luciferase reporter system, and CHIP-qPCR. The role of PVT1 in chemoresistance ability induced by hypoxia was analyzed with CCK-8 assay and flow cytometry. The roles of PVT1, hypoxia, and chemoresistance were also analyzed with LC3-GFP transfection, WB, and IHC. Finally, the results were further validated in xenograft models. PVT1 is highly expressed in lung cancer and cell lines, and the expression of PVT1 is regulated by HIF-1α, and the luciferase reporter assay and CHIP-qPCR analysis indicated that HIF-1α could bind to the promoter region of PVT1 and regulate PVT1 expression. PVT1 participated in hypoxia-induced chemoresistance and induced higher viability and lower apoptosis rate by the autophagy signaling pathway via PVT1/miR-140-3p/ATG5 axis. All the findings were validated in the xenograft models. In conclusion, these results suggest that the expression of PVT1 is regulated by HIF-1α and participates in hypoxia-induced chemoresistance.

High-fat diet induced cyclophilin B enhances STAT3/lncRNA-PVT1 feedforward loop and promotes growth and metastasis in colorectal cancer

“…Indeed, our RIPseq results here showed that CypB directly bound to lots of lncRNAs, which were enriched in signaling pathways including regulation of ER-stress, peptidyl-prolyl cis/trans isomerase (PPIase) and apoptosis, suggesting these ncRNAs may be functional as CypB itself were proved to participate in these processes [16,18,19]. After screening by integrating the sequencing results and online database, LncRNA PVT1 were chosen for further study [28,35,36], not only because it has been shown to have important oncogenic features in several types of cancer, but also because it was reported to interact directly with STAT3 in cancer cells [29]. LncRNA PVT1 transcription site is located in a cancer susceptibility locus downstream of Myc, and ablation of PVT1 from MYC-driven colon cancer line HCT116 diminished its tumorigenic potency [37].…”

Distinct transcriptomic and epigenomic modalities underpin human memory T cell subsets and their activation potential

“…6d ). Two of these genes, VBP1 and PVT1 , along with HIF1A are part of the hypoxia response 39 , 40 . Two DAR with greater accessibility in T CM , were found near the promoter region of the VBP1 gene, one of which contains a binding motif known to bind AHR (Fig.…”

miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway

“…Wu et al, 2020 also showed that miR-140-3p could enhance the sensitivity of NSCLC cells to cisplatin by targeting Wnt/β-catenin signaling to attenuate the stem cell-like properties 75 . It is worth mentioning that this study mainly focuses on the downstream pathway of miR-140-3p (ADAM10/Notch), and the upstream signal pathway of miR-140-3p is also worth studying, and there have been some research reported: Wei et al, 2022 reported that Circ_0020123 enhances the cisplatin resistance in NSCLC cells by sponging miR-140-3p/HOXB5 76 ; Wang et al, 2022 revealed that Hypoxia-induced PVT1 promotes lung cancer chemoresistance by PVT1/miR-140-3p/ATG5 axis 77 . Such research is of great significance to better understand the molecular mechanism of miR-140-3p.…”