lncRNA FOXD3‐AS1 is associated with clinical progression and regulates cell migration and invasion in breast cancer

Abstract

For women, breast cancer is the most commonly diagnosed cancer and the leading cause of women deaths due to cancer. In recent years, increasing long noncoding RNA (lncRNA) has been discovered to be related to tumorigenesis, progression, and prognosis. FOXD3-AS1 is a lncRNA and has been identified as a cancer-promoting gene in glioma. By analysing the FOXD3-AS1 expression in The Cancer Genome Atlas (TCGA) database, we found that FOXD3-AS1 has significantly high expression in breast cancer tumour comparing with the normal tissue. And patients with low FOXD3-AS1 expression had greater survival probability, smaller tumour size, and less distant metastasis. This leads us to peep inquisitively biological function of FOXD3-AS1 in breast cancer. Biological assays demonstrated that silenced FOXD3-AS1 impaired cell proliferation and inhibited cell migration and invasion in breast cancer cell lines (BT549, MDA-MB-231). These results suggest that FOXD3-AS1 could play a potential diagnostics or prognostic biomarker for patients with breast cancer. Significance of the study: We demonstrated that lncRNA FOXD3-AS1 has significantly high expression in breast cancer cell lines comparing with the normal tissue. Besides, our findings suggested that lncRNA FOXD3-AS1 could play a potential diagnostics or prognostic biomarker for patients with breast cancer. KEYWORDS FOXD3-AS1, breast cancer, invasion, lncRNA, migration 1 | INTRODUCTION Breast cancer is the first cause of new cancer diagnoses in women, approximately 30% of all new cases. And breast cancer is the second cause of leading cancer deaths; about 14% of all cancer deaths in women, the first cause is lung and bronchus cancer. From 2005 to 2014, breast cancer incidence has a slight increase. Nonwhite women promote the overwhelming majority of the increase (increases 1.7%per year among Asian and 0.3%-0.4% per year among Hispanic and black). 1,2 The higher diagnosing rate is probably because of the development of medical services and perfection of medical insurance. As the development of medical technology, significant advances have been made in the management of breast cancer. 3,4 But the death rate of breast cancer is still high, and patient outcomes still merit attention.As is known, tumorigenesis is related to the environment, living habits, aging, and so on. 5,6 But the molecular mechanisms of breast tumorigenesis still remain unclear. A lot of studies have discovered many oncogenes and tumour suppressor genes, which are acknowledged to be related to the occurrence of breast cancer. [7][8][9] Long noncoding RNAs as a heterogeneous class of noncoding RNAs, which are longer than 200 nucleotides, have been identified to involve in many human diseases, including tumorigenesis. 10,11 A few long noncoding RNAs (lncRNAs) have been identified as oncogenic or suppressor genes and regulate the progress of breast cancer. 12 lncRNA Yaoyao Guan and Adheesh Bhandari equally contributed to this study.

LncRNA FOXD3-AS1 promoted chemo-resistance of NSCLC cells via directly acting on miR-127-3p/MDM2 axis

“…FOXD3-AS1 knockdown impaired glioma cell proliferation and metastasis, suggesting the oncogenic role of FOXD3-AS1 in glioma progression [12]. FOXD3-AS1 was found to be up-regulated in breast malignant tumor and was correlated with advanced clinical stages, and silence of FOXD3-AS1 significantly attenuated the breast cancer cell proliferation and metastasis [13]. FOXD3-AS1 was abundantly expressed in both colorectal cancer (CRC) tissues and cells, FOXD3-AS1 overexpression was associated with worse clinical outcomes of CRC patients.…”

“…LncRNA EGFR antisense RNA 1 (EGFR-AS1) was found to be elevated in plasma of NSCLC patients and EGFR-AS1 overexpression promoted cisplatin resistance in NSCLC [11]. Recent evidence implied that lncRNA FOXD3 antisense RNA1 (FOXD3-AS1) was involved in the progression of different malignancies [12][13][14][15]. Unfortunately, little is known about FOXD3-AS1 regarding chemo-resistance in NSCLC.…”

Silencing of lncRNA PART1 inhibits proliferation, invasion and migration of breast cancer cells and promotes the efficacy of cisplatin in breast cancer cells

“…In the development of breast cancer, abnormal expression of multiple genes contributed to the deterioration of breast cancer. Among the abnormally expressed genes such as lncRNA CDC6, FOXD3-AS1, TRPM2-AS and POU3F3, the extremely important lncRNAs often show suppression and promotion effects on cancer cells (Guan et al 2019;Kong et al 2019;Sun et al 2019a;Yang et al 2019).…”

Long non‑coding RNA regulation of TRAIL in breast cancer: A tangle of non‑coding threads (Review)

“…Such lncRNAs are associated with cell growth suppression and apoptosis ( 87 ). High expression of lncRNA FOXD3-AS1 in cancer tissues has a direct correlation with tumor size increase and distant metastasis ( 88 ). A high level of lncRNA AWPPH in patients' plasma is associated with enhanced cell growth in early stage TNBC ( 89 ).…”