<p>LINC00662 Long Non-Coding RNA Knockdown Attenuates the Proliferation, Migration, and Invasion of Osteosarcoma Cells by Regulating the microRNA-15a-5p/Notch2 Axis</p>

Abstract

Purpose: Osteosarcoma (OS) is a frequently occurring malignancy in children and adolescents. In this study, we aimed to investigate the effects of the long non-coding RNA (lncRNA) LINC00662 (LINC00662) in OS and the underlying molecular mechanism. Methods: The expression of LINC00662, microRNA-15a-5p (miR-15a-5p), and Notch2 in OS was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, and invasion of OS cells were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound-healing, and transwell assay. The interactions among LINC00662, miR-15a-5p, and Notch2 were determined by dual-luciferase reporter assays. A tumor xenograft model was established in mice for evaluating tumor growth in vivo. Results: The expression of LINC00662 and Notch2 was found to be upregulated in OS, but the expression of miR-15a-5p was downregulated. The results demonstrated that LINC00662 knockdown attenuated the proliferation, migration, and invasion of OS cells and suppressed tumor growth in mice. The study further demonstrated that LINC00662 directly interacted with miR-15a-5p, and that Notch2 was a target of miR-15a-5p. The inhibition of miR-15a-5p or Notch2 overexpression markedly reversed the suppressive effect of sh-LINC00662 on the proliferation, migration, and invasion of OS cells. Conclusion: The study demonstrated that LINC00662 could be a potential biomarker for OS therapy, and LINC00662 knockdown suppressed the proliferation, migration, and invasion of OS cells by regulating the miR-15a-5p/Notch2 axis.

LINC00662: A new oncogenic lncRNA with great potential

“…LINC00662 is aberrantly overexpressed in tumors of the reproductive system, including cervical cancer (Wei et al, 2020), prostate cancer (N. Li et al, 2019), and breast cancer (L. Cheng, Xing, et al, 2020). LINC00662 is also significantly upregulated in glioma (Geng et al, 2020; Wu et al, 2020), lung cancer (Gong et al, 2018; Lv et al, 2021), acute myeloid leukemia (Y. Liu et al, 2019), osteosarcoma (S. Liu & Meng, 2020), melanoma (Xia et al, 2020), and chordoma (C. Wang et al, 2020).…”

Single-Cell Profiling of Tumor Microenvironment Heterogeneity in Osteosarcoma Identifies a Highly Invasive Subcluster for Predicting Prognosis

“…To study the heterogeneity among OS cells and find new cell subpopulations closely related to OS metastasis, data for 53,441 OS cells were extracted, and the cells were clustered into nine subclusters (named Osteosarcoma_0 ~ Osteosarcoma_8), and Osteosarcoma_3 and 8 were chondroblastic and the rest were osteoblastic cells ( Figure 3A and Figure S1 ). As illustrated in Figures 3B, C , the genes CADM1, LINC00662, and RUVBL1, which have been shown to inhibit OS metastasis ( 31 – 33 ), were highly expressed by the cells in subclusters 6 and 7. In addition, Osteosarcoma_8 cells showed high expression levels of COL6A1, COL6A3 and MIF, and these genes have been confirmed to be associated with metastasis ( 34 – 37 ).…”

Knockdown of lncRNA LINC00662 suppresses malignant behaviour of osteosarcoma cells via competition with miR-30b-3p to regulate ELK1 expression

“…Here, we found that sh-LINC00662 repressed the abilities of osteosarcoma cells to proliferate, migrate, and invade in vitro and inhibited the growth of tumor xenograft in vivo. In addition, Liu et al demonstrated that LINC00662 downregulation attenuates osteosarcoma progression by sponging miR-15a-5p [ 20 ]. In this study, we further determined miR-30b-3p is a target of LINC00662.…”

“…In addition, lncRNA LINC00662, located on human chromosome 19q11 [ 16 ], has been verified as an oncogene in many cancers, including gastric cancer [ 17 ], lung cancer [ 18 ] and prostate cancer [ 19 ]. Notably, a recent study conducted by Liu et al indicated that LINC00662 knockdown attenuates the proliferation, migration, and invasion of osteosarcoma cells by regulating the microRNA (miR)-15a-5p/Notch2 axis [ 20 ]. Because the pathogenesis of osteosarcoma is complex, some other downstream targets of LINC00662 are needed to be explored.…”