<p>Long Intergenic Non-Protein Coding RNA 519 Promotes the Biological Activities of Tongue Squamous Cell Carcinoma by Sponging microRNA-876-3p and Consequently Upregulating MACC1</p>

Abstract

Long intergenic non-protein coding RNA 519 (LINC00519) promotes the development of lung squamous cell carcinoma. In this study, we detected the expression of LINC00519 in tongue squamous cell carcinoma (TSCC) and examined its clinical significance. Additionally, the regulatory effects of LINC00519 on behaviors of TSCC tumor cells were explored through functional experiments. Finally, mechanistic studies were performed to elucidate the molecular events underlying the tumor-promoting actions of LINC00519 in TSCC. Materials and Methods: The expression of LINC00519 in TSCC tissues and cell lines was determined using quantitative reverse transcription-polymerase chain reaction. Cell counting kit-8 assay, flow cytometric analysis, cell migration and invasion assays and xenograft tumor model analyses were used to detect TSCC cell proliferation, apoptosis, migration and invasion and in vivo tumor growth, respectively. Mechanistic studies were performed using bioinformatics analysis, RNA immunoprecipitation assay, luciferase reporter assay and rescue experiments. Results: LINC00519 was overexpressed in both TSCC tissues and cell lines. A high LINC00519 level was associated with poor overall survival in patients with TSCC. In vitro, LINC00519 played cancer-promoting roles in TSCC progression by facilitating cell proliferation, migration and invasion and restraining cell apoptosis. In vivo, LINC00519 downregulation resulted in decreased TSCC tumor growth. Mechanistically, LINC00519 acted as a competing endogenous RNA for microRNA-876-3p (miR-876-3p), which directly targets metastasis associated with colon cancer-1 (MACC1), in TSCC cells. LINC00519 upregulated the expression of MACC1 in TSCC cells by sequestering miR-876-3p. Rescue experiments further affirmed that miR-876-3p inhibition or MACC1 overexpression mitigated the inhibitory influences of LINC00519 depletion on cell proliferation, migration and invasion and neutralized the promoting actions of LINC00519 knockdown on cell apoptosis in TSCC. Conclusion: LINC00519 aggravated the oncogenicity of TSCC by regulating the miR-876-3p/MACC1 axis. Our findings suggest that the LINC00519/miR-876-3p/MACC1 pathway may be an underlying therapeutic target in TSCC.

A Comprehensive Analysis of Pyroptosis-Related lncRNAs Signature Associated With Prognosis and Tumor Immune Microenvironment of Pancreatic Adenocarcinoma

“…LINC00519 was overexpressed and related to a poor prognosis in lung squamous cell carcinoma (LUSC) patients, which promoted tumor progression via miR-450b-5p/miR-515-5p/YAP1 pathway ( Ye et al, 2020 ). Similarly, it was also demonstrated to stimulate tumor development through miR-876-3p/MACC1 axis by serving as an emulative endogenous RNA in patients with tongue squamous cell carcinoma (TSCC) ( Liu et al, 2020 ). And LINC01133, a widely reported carcinogenic lncRNA, was shown to exert promoting effects in multiple human malignancies, which was also associated with tumor proliferation and epithelial–mesenchymal transformation (EMT) in PC ( Huang et al, 2018 ; Liu and Xi, 2020 ; Zhai et al, 2020 ; Liu et al, 2021 ; Yin et al, 2021 ; Sun et al, 2022 ).…”

Long Intergenic Non-Coding RNAs in HNSCC: From “Junk DNA” to Important Prognostic Factor

“…Long intergenic non-protein-coding RNA 519 (LINC00519) was first described in lung squamous cell carcinoma (LUSC) as an oncogene [96]. Localization analysis indicated that the vast majority of these lincRNA molecules can be found in the cytoplasm where they act as an miRNA-sequestering sponge [97]. In TSCC, one of those short RNAs is miR-876-3p, which was earlier widely described as aberrantly expressed and tumorigenic in many cancers [98].…”

“…In TSCC, one of those short RNAs is miR-876-3p, which was earlier widely described as aberrantly expressed and tumorigenic in many cancers [98]. The study based on TSCC patients with high expression of LINC00519 demonstrated shorter overall survival and unsatisfactory prognosis [97]. Although the above lincRNA displays the potential to become an HNSCC biomarker, still a lot of work remains to be done.…”

Downregulation of hsa_circTLK1 represses non-small cell lung cancer progression by regulating miR-876-3p/SRSF7 axis

“…MiR-876-3p has been reported to be involved in the progression of various cancers, including breast cancer [ 13 ], ovarian cancer [ 14 ], and colon cancer [ 15 ]. A previous study have confirmed the role of miR-876-3p in NSCLC [ 16 ], but whether circTLK1 regulates miR-876-3p remains unclear.…”