Overexpression of the lncRNA AC012213.3 Promotes Proliferation, Migration and Invasion of Breast Cancer via RAD54B/PI3K/AKT Axis and is Associated with Worse Patient Prognosis

Abstract

Background Long noncoding RNA (LncRNA) has been shown to mediate the development of human malignancies. However, data on its role in breast cancer remains scant. We aimed to evaluate the prognostic potential of lncRNAs in breast cancer. Methods We downloaded data on breast cancer patients from The Cancer Genome Atlas (TCGA) database. Tissues were obtained from The Fifth People’s Hospital of Chengdu. We then used the DESeq2 package to profile the expression of the lncRNAs between the patients and normal samples. Besides, we performed prognosis and survival analysis using survival tools in R package. We then assayed the role of the differentially expressed lncRNAs, AC012213.3 (ENSG00000266289), in cancer cell lines. Quantitative real-time PCR and Western blot analysis were performed to evaluate the expression of the gene in the cell lines and then assessed its role in the progression of breast cancer using cell proliferation (CCK8 and colony formation assays), migration, invasion (transwell and wound-healing assays) and apoptotic (flow cytometry) assays. Results Our data showed high expression of lncRNA AC012213.3 in breast cancer tissues and cell lines. The high expression of the AC012213.3 was associated with the worse prognosis and clinical features. Besides, in vitro assays demonstrated that downregulation of AC012213.3 suppresses the proliferation and invasion of breast cancer cells. Further analysis showed that RAD54B is a downstream AC012213.3 target gene and was upregulated in breast cancer. Interestingly, RAD54B expression was associated with shorter survival in breast cancer. In addition, AC012213.3 was shown to facilitate breast cancer progression through the RAD54B/PI3K/AKT axis. Conclusion Taken together, our data demonstrated that lncRNA AC012213.3 is upregulated in breast cancer and could enhance breast cancer progression through RAD54B/PI3K/AKT axis.

Prognostic Model Construction and Immune Microenvironment Analysis of Breast Cancer Based on Ferroptosis-Related lncRNAs

“…Hongmei Zhong et al proved that lncRNA AC012213.3 was highly expressed in breast cancer tissues and cell lines. 27 In addition, they also found that RAD54B was a downstream molecule of AC012213.3, overexpression of the lncRNA AC012213.3 promoted proliferation, migration and invasion of breast cancer via RAD54B/PI3K/AKT axis and was associated with worse patient prognosis. 27 However, reports on the other two high-risk lncRNAs (YTHDF3−AS1 and AC079298.3) are scarce, which needs further study.…”

“… 27 In addition, they also found that RAD54B was a downstream molecule of AC012213.3, overexpression of the lncRNA AC012213.3 promoted proliferation, migration and invasion of breast cancer via RAD54B/PI3K/AKT axis and was associated with worse patient prognosis. 27 However, reports on the other two high-risk lncRNAs (YTHDF3−AS1 and AC079298.3) are scarce, which needs further study. So far, there are few studies on ferroptosis-related lncRNAs, especially relationship between it and breast cancer needs further research, so as to find more novel therapeutic targets for breast cancer, particularly for those refractory cancer patients.…”

Role of androgen receptor signaling pathway-related lncRNAs in the prognosis and immune infiltration of breast cancer

“…The overexpression of AC012213.3 can potentially result in enhanced proliferation of BRCA cells and BRCA cell invasion. These are realized through the promotion of the process of transcription of the downstream target gene RAD54B 26 . MAPT–IT1 is associated with Koolen-De Vries syndrome 27 and can potentially predict the prognoses of patients with BRCA 28 .…”

Role of ferroptosis and ferroptosis-related long non'coding RNA in breast cancer

“…In this study, three genes, lncRNAs YTHDF3-AS1, AC079298.3 and AC012213.3, which are overexpressed in at-risk populations, were screened, indicating that they may be at-risk oncogenes for BC. In addition, lncRNA NC012213.3, a downstream molecule of AC012213.3, and overexpressed LncRNA AC012213.3 promotes BC multiplication, invasion and invasiveness through the RAD54B/PI3K/AKT axis and is associated with poor patient outcomes [ 193 ]. However, studies on YTHDF3-AS1 and AC079298.3 are limited and require further investigation.…”