Knockdown of LINC00665 inhibits proliferation and invasion of breast cancer via competitive binding of miR-3619-5p and inhibition of catenin beta 1

Abstract

Background Long intergenic non-protein coding RNA00665 (LINC00665) plays a crucial tumorigenic role in many cancers, such as gastric cancer and lung adenocarcinoma. However, its role and mechanism of action in the progression of breast cancer (BC) are unknown. Methods LINC00665 expression levels were determined using quantitative polymerase chain reaction analysis with BC tissues and cell lines. BC cell proliferation was tested by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, whereas BC cell migration and invasion capabilities were analyzed by performing transwell migration assays. Percentages of apoptotic cells were measured by flow cytometry. Interactions between LINC00665 and miR-3169-5p were examined by performing luciferase reporter assays, and the expression levels of proteins, such as β-catenin, were examined by western blot analysis. Results LINC00665 was expressed at high levels in BC tissues and cells. Upregulated LINC00665 expression correlated with tumor size and tumor, node, and metastasis stages, but not with the age of patients. LINC00665 knockdown inhibited BC cell proliferation, migration, and invasion, whereas it promoted apoptosis. Moreover, bioinformatics analysis and the luciferase reporter assay revealed that LINC00665 bound the microRNA (miR) miR-3619-5p. miR-3619-5p expression correlated negatively with LINC00665 expression in BC tissues. miR-3619-5p overexpression inhibited BC cell proliferation, migration, and invasion, but promoted apoptosis. Simultaneous knockdown of LINC00665 and miR-3619-5p led to increased cell proliferation, migration, and invasion, and inhibited apoptosis. Additionally, catenin beta 1, which encodes the β-catenin protein, was the target gene of miR-3619-5p. β-catenin expression clearly decreased after LINC00665 knockdown and miR-3619-5p overexpression, but increased after simultaneous knockdown of LINC00665 and miR-3619-5p. Conclusion LINC00665 knockdown inhibited BC cell proliferation and invasion by binding miR-3619-5p and inhibiting β-catenin expression.

LINC00665 Targets miR-214-3p/MAPK1 Axis to Accelerate Hepatocellular Carcinoma Growth and Warburg Effect

“…One of the mechanisms by which lncRNAs are implicated in tumorigenesis is acting as competing endogenous RNAs (ceRNA) of microRNA (miRNA) and thereby facilitating the transcription of target mRNAs [ 12 , 13 ]. Up to now, long intergenic non-protein-coding RNA 665 (LINC00665) has been found to show a higher expression pattern in cancers and to be closely implicated in carcinogenesis, including breast cancer [ 14 ], prostate cancer [ 15 ], gastric cancer [ 16 ], colorectal cancer [ 17 ], and ovarian cancer [ 18 ]. Shan et al [ 19 ] found that LINC00665 level was increased in HCC tissues and cells and associated with shorter overall survival, and depletion of LINC00665 repressed cell viability and promoted cell apoptosis and autophagy in HCC via the miR-186-5p/MAP4K3 axis.…”

Linc00665 Can Predict the Response to Cisplatin-Paclitaxel Neoadjuvant Chemotherapy for Breast Cancer Patients

“…Previous studies have shown that overexpression of Linc00665 can enhance the invasion and metastasis of various tumors, which supports our speculation. Yu et al reported that Linc00665 deletion can inhibit the migration and invasion of triple negative breast cancer cell lines MDA-MB-231 and BT549 ( 12 , 31 ). Gao et al elucidated that Linc00665 knockdown can inhibit the migration and invasion of gastric cancer cell lines AGS and BGC‐823 ( 9 ).…”

The Emerging Roles of LINC00665 in Human Cancers

“…Lu et al analyzed the expression level of LINC00665 in breast cancer tissues and matched normal tissues in the database ( Lv et al, 2020 ). They found that the expression of the LINC00665 was significantly upregulated in breast cancer tissues ( Lv et al, 2020 ).…”

“…Lu et al analyzed the expression level of LINC00665 in breast cancer tissues and matched normal tissues in the database ( Lv et al, 2020 ). They found that the expression of the LINC00665 was significantly upregulated in breast cancer tissues ( Lv et al, 2020 ). Subsequently, they used qRT-PCR to identify LINC00665 expression in 106 pairs of breast cancer tissues and adjacent normal tissues and also proved that LINC00665 was highly expressed in breast cancer tissues ( Lv et al, 2020 ).…”