क्लिनिकल परीक्षण जर्नल
खुला एक्सेस

अमूर्त

LINC00115 Promote the Invasion and Metastasis of Lung Adenocarcinoma via the IL6/JAK1/STAT1 Signaling Pathway

Li Li, Linlin Fan, Huifang Cai, Hui qin Song, Hai tao Wei

Background: Lung Adenocarcinoma (LUAD) is an important subtype of lung cancer with a high incidence and mortality. LncRNA play a vital role in the occurrence and development of various cancers, including LUAD. LINC00115 was found to be highly expressed in Glioblastoma, breast cancer and colorectal cancer tissues compared with para-carcinoma tissue, and certified to regulate tumor cell proliferation, apoptosis, cell cycle, invasion and migration. However, the molecular mechanism of LINC00115 in lung adenocarcinoma still remains unclear.

Methods: 72 pairs of fresh cancerous and paracancerous tissues were investigated by PCR and RT-qPCR. The diagnostic value of LINC00115 in lung adenocarcinoma was analyzed by ROC curve. Cytological experiment in vitro was detected by cell counting kit-8 (CCK-8) experiment, clone formation assay, cell scratch test, flow cytometric apoptosis and cycle assay, and transwell assay (for cell invasion and cell migration). Besides, the proliferation and invasion and metastasis of LINC00115 cells in vivo were tested by subcutaneous tumor bearing and tail vein injection in nude mice. Ln CATLAS database and RNA Fluorescence in Situ Hybridization (FISH) assay are used to predict subcellular localization of LINC00115. RNA pull-down assay and MS analysis were used to identify LINC00115 binding proteins (RBPs). Names and binding sites of LINC00115 binding proteins were confirmed by cat RAPID and ENCORI database. Binding protein of LINC00115 was detected by Western Blot (WB) assay.

Results: LINC00115 was upregulated in lung adenocarcinoma compared with para-carcinoma tissue. LINC00115 was closely correlated with TNM staging and lymph node metastasis in patients with lung adenocarcinoma, and was negatively correlated with patients' age, gender, tumor size, smoking or not. The Receiver Operating Characteristic (ROC) curve analysis was a high diagnostic value of LINC00115 for patients with lung adenocarcinoma. Nude mice model of pulmonary metastasis via tail vein injection was performed to knock-downed LINC00115 had significantly inhibited on the invasion and metastasis of lung adenocarcinoma compared with the control group. LINC00115 was located in the cytoplasm. LINC00115 directly binds to the KHSRP protein. The result of RT-PCR that LINC00115 promoted the invasion and metastasis of lung adenocarcinoma via IL6/JAK1/STAT1 signaling pathway.

Conclusions: LINC00115 directly recruits KHSRP protein to promot the invasion and metastasis in lung adenocarcinoma via IL6/JAK1/STAT1 signaling pathway. Our findings provided a new biomarker and potential therapeutic targets for clinical diagnosis of lung adenocarcinoma.