LINC00294 promotes proliferation, invasion, and migration of breast cancer cells via AKT/mTOR/HIF-1α pathway

To explore the changes in the expression of long non-coding RNA（LncRNA）LINC00294 in breast cancer tissues and cells, and investigate its effects and the possible mechanisms on the biological properties of breast cancer cells.

The differentially expressed genes（DEGs）were analyzed using transcriptome sequencing data from 41 breast cancer tissues and 11 para-cancerous tissues from the Gene Expression Omnibus（GEO）database（GSE45827）. Then qRT-PCR assay was used to measure the expression of LINC00294 in 20 pairs of breast cancer and para-cancerous tissues from the breast cancer patients diagnosed in our department, as well as in the normal human breast epithelial MCF-10A cells and the human breast cancer cell lines MCF-7, K-BR-3 and MDA-MB-231. After MCF-7 cells were transfected with lentiviral vector of si-LINC to interfere LINC00294 expression, CCK-8 assay was used to detect cell proliferation, flow cytometry and Western blotting were employed to measure cell apoptosis and expression of related proteins, cell scratch assay and Transwell assay were applied to observe cell migration and invasion. Then, the effect of interference with LINC00294 on tumor growth in nude mice model of in situ subcutaneous tumorigenesis was observed. The expression of AKT/mTOR pathway-related proteins p-mTOR, mTOR, p-AKT, AKT, and its downstream target molecule HIF-1α was detected by Western blotting.

LncRNA LINC00294 was screened out as a DEG in breast cancer tissues from the GEO database. It was also highly expressed in breast cancer tissues and MCF-7, SK-BR-3 and MDA-MB-231 cells（P<0.05）. Interference of LINC00294 resulted in reduced proliferation, enhanced expression of apoptosis-related proteins, and decreased invasion and migration abilities in MCF-7 cells（P<0.05）. The expression of LINC00294 was inhibited by HIF-1α interference（P<0.05）, and LINC00294 interference decreased the expression of p-AKT, p-mTOR, mTOR and its downstream target molecule HIF-1α in the AKT/mTOR signaling pathway（P<0.05）.

High expression of LINC00294 in breast cancer may affect the proliferation, invasion, and migration of breast cancer through the AKT/mTOR/HIF-1α signaling pathway, and LINC00294 may be closely associated with the pathogenesis of breast cancer.