Linc00996 is a favorable prognostic factor in LUAD: Results from bioinformatics analysis and experimental validation

Zhenghai Shen; Xin Li; Zaoxiu Hu; Yanlong Yang; Zhenghong Yang; Shanshan Li; Yongchun Zhou; Jie Ma; Hongsheng Li; Xi Liu; Jingjing Cai; Lisa Pu; Xiaoxiong Wang; Yunchao Huang

doi:10.3389/fgene.2022.932973

Linc00996 is a favorable prognostic factor in LUAD: Results from bioinformatics analysis and experimental validation

Front Genet. 2022 Sep 2:13:932973. doi: 10.3389/fgene.2022.932973. eCollection 2022.

Authors

Zhenghai Shen^{1

2

3}, Xin Li⁴, Zaoxiu Hu⁵, Yanlong Yang⁶, Zhenghong Yang³, Shanshan Li³, Yongchun Zhou^{1

2}, Jie Ma¹, Hongsheng Li², Xi Liu^{1

2}, Jingjing Cai², Lisa Pu⁷, Xiaoxiong Wang², Yunchao Huang³

Affiliations

¹ Cancer Center Office, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, China.
² Molecular Diagnosis Sub Center of Yunnan Cancer Center, Yunnan Cancer Molecular Diagnosis Center, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, China.
³ Department of Thoracic Surgery I, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, China.
⁴ Department of Clinical Laboratory, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, China.
⁵ Department of Pathology, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), Kunming, China.
⁶ Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
⁷ Department of Nephrology, Kunming Yanan Hospital, Kunming, China.

Abstract

Background: Linc00996 has been reported in a variety of malignant tumors, but its potential role and significance in lung adenocarcinoma (LUAD) are not fully understood. The authors investigated the expression and biological behavior of Linc00996 in LUAD and elucidated the function of its potential target genes. Materials and methods: The data of Linc00996 expression in cancers were derived from GEPIA. GEO and TCGA datasets were used to identify the differential expression of Linc00996 in LUAD and analyze the respective correlation between different expression levels and LUAD stage and survival prognosis. We further elucidated the potential biological processes and pathways involved with Linc00996 in LAUD by GSEA. ssGSEA was applied to explore the relationship between Linc00996 and immune activity. Finally, the clinical impact of Linc00996 was assessed in 61 patients with LUAD, and the biological functions of Linc00996 were determined by a series of experiments in vitro, such as CCK8, colony formation, migration, and invasion assays. Results: Compared with adjacent normal lung tissues, Linc00996 was significantly downregulated in LUAD, and its expression was negatively correlated with T stage, N stage, and pathological stage. An in vitro study suggested that enhanced Linc00996 expression could inhibit cell proliferation, clonal formation, migration, and invasion in LUAD cell lines. Via GSEA and ssGSEA, we observed that Linc00996 might be connected with immune infiltration in LUAD, and Linc00996 might inhibit tumorigenesis and metastasis by regulating antigen processing and presentation, JAK-STAT3, and cell adhesion molecular signaling pathways. Conclusion: Linc00996 is a novel tumor suppressor in LUAD and may suppress the tumorigenesis and metastasis of LUAD via the tumor-related signaling pathway, such as antigen processing and presentation, JAK-STAT3, and cell adhesion molecular signaling pathways.

Keywords: LUAD; Linc00996; bioinformatics; lncRNA; prognosis.