LncRNA FGD5-AS1 Facilitates the Radioresistance of Breast Cancer Cells by Enhancing MACC1 Expression Through Competitively Sponging miR-497-5p

Abstract

BackgroundLncRNA-FGD5-AS1, as an oncogene, participates in the development and progress of various cancers. However, the exact role and the molecular mechanisms by which FGD5-AS1 regulates radiosensitivity in breast cancer (BC) remains largely unknown.MethodsWe used X-Ray weekly-dose-increase method to establish radiation-resistance cell lines. Bioinformatics tools analyze the expression of FGD5-AS1 in breast cancer tissue and evaluated the relationship between FGD5-AS1 and clinic-pathological features. CCK-8 and colony formation were used to analyze cell proliferation. Western blotting and qPCR were applied to detect protein and gene expression, respectively. RNA interference was used to knock down the endogenous gene expression. Luciferase reporter system and immunoprecipitates were applied to verify the target of FGD5-AS1.ResultFGD5-AS1 was overexpressed in BC tissues and radiation-resistance cell lines. Higher levels of FGD5-AS1 predicted poorer clinical characteristics and prognosis. Loss-of-function FGD5-AS1 sensitized BC cells to X-ray, meanwhile, the cell gained radiation-resistance when exogenous FGD5-AS1 was expressed. FGD5-AS1 depletion arrested cells at G0/G1 and triggers cell apoptosis. The starBase database (ENCORI), predicted binding site of miR-497-5p in FGD5-AS1 sequence, and luciferase reporter system and immunoprecipitates verified miR-497-5p was the target of FGD5-AS1. Furthermore, MACC1 was predicted and verified as the target of miR-497-5p. Loss-of-function FGD5-AS1 sensitized ionizing radiation was rescued by the up-regulation of MACC1 and the inhibition of miR-497.ConclusionFGD5-AS1 displays an oncogene profile in CRC; patients with high expression of FGD5-AS1 should benefit less from radiotherapy and need a more frequent follow-up. Besides, FGD5-AS1 may be a potential therapeutic target for CRC.

The role of long non-coding RNA FGD5-AS1 in cancer

“…FGD5-AS1 is significantly overexpressed in breast cancer tissues and cells and could promote the proliferation, glycolysis, migration, and invasion of BC cells by binding with miR-195-5p and removing the inhibitory effect on NUAK2 expression; moreover, silencing FGD5-AS1 leads to the opposite phenotype [ 45 ]. Li et al [ 23 ] also confirmed the above results and found that FGD5-AS1 can competitively bind with miR-497-5p, which promotes the expression of MACC1 and the radiotherapy tolerance of BC cells. Furthermore, FGD5-AS1 deficiency could promote breast cancer cell apoptosis and sensitize the cells to X-rays by activating the expression of BAX, Caspase 3, and Caspase 9 [ 23 ].…”

“…Li et al [ 23 ] also confirmed the above results and found that FGD5-AS1 can competitively bind with miR-497-5p, which promotes the expression of MACC1 and the radiotherapy tolerance of BC cells. Furthermore, FGD5-AS1 deficiency could promote breast cancer cell apoptosis and sensitize the cells to X-rays by activating the expression of BAX, Caspase 3, and Caspase 9 [ 23 ]. These results indicate that FGD5-AS1 plays an important role in the progression of BC.…”

“…LncRNA-FGD5-AS1 is a newly discovered lncRNA that has attracted considerable from researchers. Abnormally high expression of FGD5-AS1 has been reported in lung cancer [ 21 , 39–42 ], liver cancer [ 34 , 35 ], cervical cancer [ 53 ], osteosarcoma [ 69 , 70 ], glioma cancer [ 61–64 ], colorectal cancer [ 22 , 37 ], oral cancer [ 28 , 29 ], ovarian cancer [ 55 , 56 ], breast cancer [ 23 , 45 ], gastric cancer [ 30 , 31 ], pancreatic cancer [ 73 ], melanoma [ 72 ], and laryngeal squamous cell carcinoma [ 71 ] and is associated with poor prognosis in these cancers. However, several studies have also reported that FGD5-AS1 inhibits cancer.…”

Identification and functional analysis of N6‐methyladenine (m6A)‐related lncRNA across 33 cancer types

“…Li et al found that lncRNA FGD5-AS1 was overexpressed in breast cancer tissues and predicted poorer clinical characteristics and prognosis. 51 This study demonstrated that most m 6 A-related ln-cRNA FGD5-AS1 was associated with cisplatin resistance, by competitively binding to has-miR-362-3p in BRCA patients. In another case, Hu et al revealed that IGF2BP2 served as an m 6 A reader to regulate lncRNA DANCR, thereby promoting cancer stemness-like properties and pathogenesis.…”

LncRNAs as Theragnostic Biomarkers for Predicting Radioresistance in Cancer: A Systematic Review and Meta-Analysis

“…The included studies in the current systematic review and meta-analysis were published between 2015 and 2020 and conducted in Canada and China. The sources of the malignant tumor included glioma ( 35 , 36 , 38 , 41 , 43 ), neck squamous carcinoma (HNSCC) ( 57 ), esophageal cancer (EC) ( 22 ), breast cancer ( 34 , 42 , 46 , 47 ), colorectal cancer ( 39 , 58 ), non-small cell lung cancer (NSCLC) ( 40 , 45 , 50 – 52 ), ovarian cancer (OC) ( 48 ), cardiac carcinoma ( 49 ), thyroid carcinoma ( 44 ), prostate cancer ( 54 ), and nasopharyngeal carcinoma (NPC) ( 37 , 56 ). Sample sizes included in these studies varied from 31 to 955 between the studies.…”