Downregulation of circ<scp>ATXN7</scp> represses non‐small cell lung cancer growth by releasing mi<scp>R</scp>‐7‐5p

Li, Dongliang; Fu, Zejun; Dong, Chen; Song, Yongming

doi:10.1111/1759-7714.14426

Cited by 8 publications

(3 citation statements)

References 34 publications

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“…PFN2 participates in cell shape alternations and cell movement via regulating polymerization and reorganization of the actin cytoskeleton. PFN2 acts as an oncogene in NSCLC [ 24 – 26 ]. In the present study, silencing of circ-SLC16A1 reduced expression of PFN2.…”

Section: Discussionmentioning

confidence: 99%

Oncogenic circ-SLC16A1 promotes progression of non-small cell lung cancer via regulation of the miR-1287-5p/profilin 2 axis

Jin,

Yuan,

Tian

et al. 2024

Cell Mol Biol Lett

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Background Circular RNAs (circRNAs) are single-stranded RNAs with covalently closed structures that have been implicated in cancer progression. However, the regulatory mechanisms remain largely unclear. So, the aim of this study was to reveal the role and regulatory mechanisms of circ-SLC16A1. Methods In this study, next-generation sequencing was used to identify abnormally expressed circRNAs between cancerous and para-carcinoma tissues. Fluorescence in situ hybridization and quantitative reverse transcription polymerase chain reaction were performed to assess the expression patterns of circ-solute carrier family 16 member 1 (SLC16A1) in non-small cell lung cancer (NSCLC) cells and tissue specimens. The dual-luciferase reporter assay was utilized to identify downstream targets of circ-SLC16A1. Transwell migration, wound healing, 5-ethynyl-2′-deoxyuridine incorporation, cell counting, and colony formation assays were conducted to assess the proliferation and migration of NSCLC cells. A mouse tumor xenograft model was employed to determine the roles of circ-SLC16A1 in NSCLC progression and metastasis in vivo. Results The results found that circ-SLC16A1 was upregulated in NSCLC cells and tissues. Downregulation of circ-SLC16A1 inhibited tumor growth by reducing proliferation, lung metastasis, and lymphatic metastasis of NSCLC cells, and arrested the cell cycle in the G1 phase. Also, silencing of circ-SLC16A1 promoted apoptosis of NSCLC cells. The results of bioinformatics analysis and the dual-luciferase reporter assay confirmed that microRNA (miR)-1287-5p and profilin 2 (PFN2) are downstream targets of circ-SLC16A1. PFN2 overexpression or circ-SLC16A1 inhibition restored proliferation and migration of NSCLC cells after silencing of circ-SLC16A1. PFN2 overexpression restored migration and proliferation of NSCLC cells post miR-1287-5p overexpression. Conclusions Collectively, these findings show that miR-1287-5p/PFN2 signaling was associated with downregulation of circ-SLC16A1 and reduced invasion and proliferation of NSCLC cells. So, circ-SLC16A1 is identified as a mediator of multiple pro-oncogenic signaling pathways in NSCLC and can be targeted to suppress tumor progression.

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Section: Discussionmentioning

confidence: 99%

Oncogenic circ-SLC16A1 promotes progression of non-small cell lung cancer via regulation of the miR-1287-5p/profilin 2 axis

Jin,

Yuan,

Tian

et al. 2024

Cell Mol Biol Lett

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“…[21] Li et al stated that circATXN7 accelerated tumor metastasis and growth via miR-7-5p sponging effect in lung cancer. [22] CircRNA_0082835 facilitated cell progression and lymphatic metastasis via sequestering miR-429 in primary melanoma. [23] Also, upregulated miR-25-3p might reverse circ_PRDM5-induced inhibitory effects on BC cells.…”

Section: Circ_prdm5 Inhibited Bc Cell Malignant Progression By Target...mentioning

confidence: 99%

Circ_PRDM5/miR‐25‐3p/ANKRD46 axis is associated with cell malignant behaviors in subjects with breast cancer evaluated by ultrasound

Sun

et al. 2023

J Biochem & Molecular Tox

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Circular RNAs (circRNAs) are key RNA molecules in cancer biology. CircRNA PR/SET domain 5 (circ_PRDM5, hsa_circ_0005654) was downregulated in breast cancer (BC) tissues. This study is designed to investigate the functional mechanism of circ_PRDM5 in BC. Ultrasound examinations were performed to evaluate BC patients and normal individuals. Circ_PRDM5, miR‐25‐3p, and Ankyrin repeat domain 46 (ANKRD46) level detection was carried out by reverse transcription‐quantitative polymerase chain reaction. 3‐(4, 5‐dimethylthiazol‐2‐y1)‐2, 5‐diphenyl tetrazolium bromide (MTT) assay was used for cell viability examination. Cell proliferation was evaluated by ethynyl‐2′‐deoxyuridine assay and colony formation assay. The protein levels were examined using western blot. Cell migration and invasion abilities were assessed via transwell assay. Target interaction was analyzed via dual‐luciferase reporter assay. The role of circ_PRDM5 in vivo was explored via xenograft tumor assay. Circ_PRDM5 expression was downregulated in BC tissues and cells. Overexpression of circ_PRDM5 suppressed proliferation and motility but enhanced apoptosis of BC cells. Circ_PRDM5 served as a sponge of miR‐25‐3p. Circ_PRDM5 impeded BC cell malignant development via sponging miR‐25‐3p. Circ_PRDM5 induced ANKRD46 upregulation by targeting miR‐25‐3p. Inhibition of miR‐25‐3p retarded BC progression by increasing the ANKRD46 level. Circ_PRDM5 repressed BC tumorigenesis in vivo through mediating the miR‐25‐3p/ANKRD46 axis. This study evidenced that circ_PRDM5 inhibited cell progression and tumor growth in BC via interacting with mir‐25‐3p/ANKRD46 network.

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“…PFN2 was highly expressed in lung cancer. It was upregulated by the circular RNA (circRNA) ataxin 7 (circATXN7) to accelerate the malignant progression of non-small cell lung cancer (NSCLC) [14]. It was also targeted by miR-30a-5p, which results in inhibition of epithelial-mesenchymal transition (EMT) in highly invasive NSCLC cell lines [15].…”

Section: Introductionmentioning

confidence: 99%

Profilin 2 regulates pyruvate kinase M2 nuclear translocation and potentiates tumor angiogenesis in non-small cell lung cancer

et al. 2023

Preprint

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Profilin 2 (PFN2) is an actin-binding protein important for cancer initiation and progression. However, the function and precise role of PFN2 in non-small cell lung cancer (NSCLC) remain unclear. Here, we assessed the expression levels of PFN2 in tissue from patients with NSCLC; identified binding partners using mass spectrometry, co-immunoprecipitations, and molecular modeling; and studied the angiogenic-promoting function of PFN2 using 3D droplet cultures and tube-formation assays. We found that upregulated PFN2 expression is associated with poor prognosis in patients with NSCLC. Knockdown of PFN2 significantly impaired the proliferation and angiogenesis of NSCLC cells, both in vivo and in vitro. Mechanistically, PFN2 physically interacts with pyruvate kinase M2 (PKM2) and modulates extracellular-signal regulated kinase 1/2 (ERK1/2)-mediated phosphorylation of PKM2 at S37, which substantially increases its nuclear translocation. PFN2 knockdown lead to reduced expression of PKM2, p65-NF-κB, and hypoxia-inducible factor (HIF)-1α and inhibited the nuclear translocation of PKM2. This resulted in impaired formation of the PKM2-HIF-1α-p65-NF-κB transcription complex, leading to decreased expression of its downstream target genes VEGFA, CCND1, and MAP2K5. Moreover, mutations in PFN2 at Y134 or S138 impaired its binding to PKM2, nuclear translocation of PKM2, and functionally inhibited angiogenesis in lung cancer cells. Overall, our data provide insights into the role of PFN2 in the regulation of lung cancer angiogenesis and indicate that PFN2 may serve as a therapeutic target against NSCLC.

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Downregulation of circATXN7 represses non‐small cell lung cancer growth by releasing miR‐7‐5p

Cited by 8 publications

References 34 publications

Oncogenic circ-SLC16A1 promotes progression of non-small cell lung cancer via regulation of the miR-1287-5p/profilin 2 axis

Oncogenic circ-SLC16A1 promotes progression of non-small cell lung cancer via regulation of the miR-1287-5p/profilin 2 axis

Circ_PRDM5/miR‐25‐3p/ANKRD46 axis is associated with cell malignant behaviors in subjects with breast cancer evaluated by ultrasound

Profilin 2 regulates pyruvate kinase M2 nuclear translocation and potentiates tumor angiogenesis in non-small cell lung cancer

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