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LINC00467 facilitates osteosarcoma progression by sponging miR?217 to regulate KPNA4 expression.

ABSTRACT: Osteosarcoma (OS) is a musculoskeletal malignancy that originates from interstitial cells. An increasing number of studies have verified that long non?coding RNAs (lncRNAs) participate in the progression of numerous types of cancer. It has been reported that LINC00467 is a cancer?promoting gene in some types of cancer; however, the regulatory mechanism of LINC00467 in OS remains unknown. In the present study, reverse transcription-quantitative PCR was used to determine LINC00467 expression in OS tissues and cells. Additionally, the impact of LINC00467?knockdown on OS cell proliferation, migration and invasion was analyzed using Cell Counting Kit?8, colony formation and Transwell assays, as well as western blot analysis. RNA pulldown and luciferase reporter assays were conducted to investigate the regulatory mechanism of LINC00467 in OS. The results delineated that LINC00467 expression was elevated in OS tissues and cells, and that high LINC00467 expression was associated with a poor prognosis in patients with OS. LINC00467 inhibition suppressed OS progression by inhibiting cell proliferation, migration, invasion and epithelial?mesenchymal transition. LINC00467 served as a molecular sponge for microRNA (miR)?217, while karyopherin subunit ?4 (KPNA4) was a downstream target gene of miR?217. Moreover, the overexpression of KPNA4 reversed the inhibitory effects of LINC00467 inhibition on OS progression. Therefore, the present study elucidated the potential mechanism of LINC00467 in OS and indicated that LINC00467 exerted its carcinogenic effects on OS through the miR?217/KPNA4 axis, implying that LINC00467 may be a novel potential therapeutic target for OS.

SUBMITTER: Yan J

PROVIDER: S-EPMC7895521 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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LINC00467 facilitates osteosarcoma progression by sponging miR‑217 to regulate KPNA4 expression.

Yan Jing J Fang Tao T Zhang Ming M Zhou Quan Q

International journal of molecular medicine 20210204 3

Osteosarcoma (OS) is a musculoskeletal malignancy that originates from interstitial cells. An increasing number of studies have verified that long non‑coding RNAs (lncRNAs) participate in the progression of numerous types of cancer. It has been reported that LINC00467 is a cancer‑promoting gene in some types of cancer; however, the regulatory mechanism of LINC00467 in OS remains unknown. In the present study, reverse transcription-quantitative PCR was used to determine LINC00467 expression in OS ...[more]

PMID: 33537823

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Project description:BackgroundPrevious data have suggested that ginsenoside Rg3 (Rg3), isolated from the roots of Panax ginseng, plays a repressing role in multiple cancers, including osteosarcoma (OS). However, there is no any literature available about the role of circular RNA (circRNA) in Rg3-mediated OS development. The study aimed to explore the function of circ_0003074 in the anti-cancer effects of Rg3 on OS.MethodsRNA expression of circ_0003074, miR-516b-5p and karyopherin subunit alpha 4 (KPNA4) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was evaluated by Western blotting or immunohistochemistry assay. Cell viability, proliferation, apoptosis, migration and invasion were investigated by cell counting kit-8, 5-ethynyl-29-deoxyuridine (EdU), flow cytometry analysis, wound-healing and transwell invasion assays, respectively. Dual-luciferase reporter and/or RNA immunoprecipitation assay was performed to confirm the interplay between miR-516b-5p and circ_0003074 or KPNA4. Xenograft mouse model assay was conducted to reveal the effect of Rg3 treatment on tumor formation.ResultsCirc_0003074 and KPNA4 expression was significantly upregulated, while miR-516b-5p was downregulated in OS tissues and cells compared with controls. Rg3 treatment dramatically decreased circ_0003074 expression in OS cells. Rg3 treatment led to decreased cell proliferation, migration and invasion but increased cell apoptosis, which was attenuated after circ_0003074 overexpression. Besides, miR-516b-5p was a target miRNA of circ_0003074 and partially restored circ_0003074-mediated action under Rg3 treatment. Decreasing miR-516b-5p expression also promoted Rg3-treated OS cell malignancy through KPNA4, which was identified as a target mRNA of miR-516b-5p. Besides, circ_0003074 induced KPNA4 production owing to the decrease of miR-516b-5p expression. Furthermore, Rg3 treatment inhibited tumor formation by regulating circ_0003074 in vivo.ConclusionRg3 inhibited OS progression through circ_0003074/miR-516b-5p/KPNA4 axis, showing the potential of Rg3 as a therapeutic agent for OS.

Dataset Information

LINC00467 facilitates osteosarcoma progression by sponging miR?217 to regulate KPNA4 expression.

Publications

LINC00467 facilitates osteosarcoma progression by sponging miR‑217 to regulate KPNA4 expression.

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