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MiR?7/SP1/TP53BP1 axis may play a pivotal role in NSCLC radiosensitivity.

ABSTRACT: MicroRNA?7 (miR?7) has been identified as a tumor suppressor in non?small cell lung cancer (NSCLC) and a radiosensitivity regulator. Numerous studies have revealed that specific protein 1 (SP1) plays a critical role in the tumorigenesis of various types of cancers and regulates radiosensitivity and tumor suppressor p53?binding protein 1 (TP53BP1), which plays an essential role in DNA repair. However, it is not clear whether miR?7 has a regulatory effect on SP1 and TP53BP1 in NSCLC. In the present study it was revealed that miR?7 directly binds to the 3'UTR of SP1, thereby suppressing SP1 expression to regulate radiosensitivity. Overexpression of miR?7 and SP1 and knockdown of miR?7 and SP1 were performed using lentiviral transfection. Protein and mRNA abundance of SP1 and TP53BP1 were determined using western blotting and RT?qPCR, respectively, while miR?7 binding to SP1 was validated using a luciferase reporter assay. Biological function analysis indicated that miR?7 negatively regulated SP1 and inhibited cell proliferation, migration, and invasion when combined with radiation. It was also revealed that the expression of TP53BP1 was positively regulated by SP1 or negatively regulated by miR?7. In conclusion, SP1 was a target of miR?7, and the decreased expression of SP1 resulting from miR?7 overexpression in NSCLC was vital for improving radiosensitivity in NSCLC cells. Moreover, SP1 expression was detected in 95 paired NSCLC and adjacent normal tissues, and it was determined that SP1 was significantly upregulated in NSCLC tissues and that its upregulation was correlated with the degree of tissue differentiation. Thus, SP1 and/or miR?7 may be potential molecular targets in NSCLC radiotherapy.

SUBMITTER: Guo G

PROVIDER: S-EPMC7640372 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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miR‑7/SP1/TP53BP1 axis may play a pivotal role in NSCLC radiosensitivity.

Guo Genyan G Li Lingling L Song Guanchu G Wang Jie J Yan Ying Y Zhao Yuxia Y

Oncology reports 20201023 6

MicroRNA‑7 (miR‑7) has been identified as a tumor suppressor in non‑small cell lung cancer (NSCLC) and a radiosensitivity regulator. Numerous studies have revealed that specific protein 1 (SP1) plays a critical role in the tumorigenesis of various types of cancers and regulates radiosensitivity and tumor suppressor p53‑binding protein 1 (TP53BP1), which plays an essential role in DNA repair. However, it is not clear whether miR‑7 has a regulatory effect on SP1 and TP53BP1 in NSCLC. In the presen ...[more]

PMID: 33125142

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Project description:BackgroundCircular RNAs (circRNAs) are endogenous non-coding RNAs, which are associated with various biological processes, including microRNA (miRNA) interaction, protein binding and regulatory splicing. circRNA_0005529 (circ_0005529) is derived from vacuolar protein sorting 33 homologue B (VPS33B), and its biological role in gastric cancer (GC) has not been examined. In this study, the expression and location of circ_0005529 and microRNA-527 (miR-527) were determined by qRT-PCR and fluorescence in situ hybridization (FISH). Cell proliferation and cell migration were determined by MTT, EdU incorporation, colony formation, wound scratch and transwell assays. In addition, immunohistochemistry and western blotting were performed to determine the expressions of specificity protein 1 (Sp1), PCNA, c-myc, E-cadherin and N-cadherin. Western blotting and luciferase reporter assay were performed to study the interaction between circ_0005529 and miR-527 or miR-527 and Sp1. The functional effects of circ_0005529 on GC through regulating Sp1 were further evaluated using xenograft and metastatic mouse models in vivo.ResultsOur results showed that circ_0005529 was upregulated in GC tissues and cells, and had promoting effects on cell proliferation and cell migration. Mechanism analysis suggested that circ_0005529 could bind to microRNA-527 (miR-527) and reduce its expression. The interaction between miR-527 and Sp1 in GC was systematically studied. In addition, the results indicated that Sp1 upregulation could rescue the effects on cell proliferation and migration caused by circ_0005529. Moreover, the inhibitory effects of circ_0005529 downregulation on GC growth and metastasis were evaluated in mouse models. These findings suggested that the axis of circ_0005529/miR-527/Sp1 may serve as a promising treatment target for GC diagnosis and treatment.ConclusionsThese findings suggested that the signal axis of circ_0005529/miR-527/Sp1 may has the potential to be explored as a novel therapeutic target for GC diagnosis and treatment. Mechanism diagram: During GC development, overexpressed circ_0005529 sponged miR-527 and then upregulated the expression of Sp1. Subsequently, epithelial-mesenchymal transition (EMT), cell proliferation and cell migration were promoted, which ultimately facilitated the tumor metastasis.

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MiR?7/SP1/TP53BP1 axis may play a pivotal role in NSCLC radiosensitivity.

Publications

miR‑7/SP1/TP53BP1 axis may play a pivotal role in NSCLC radiosensitivity.

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