Long non-coding RNA (LncRNA) CASC9/microRNA(miR)-590–3p/sine oculis homeobox 1 (SIX1)/NF-κB axis promotes proliferation and migration in breast cancer

Abstract

Long non-coding RNA (lncRNA)–microRNA–mRNA signaling axes have recently been shown to have a key role in the development of breast cancer (BC). In this study, we investigated how the cancer susceptibility candidate 9 (CASC9) gene affects the cell growth, invasion, migration, and apoptosis of BC cells. The levels of microRNA-590-3p (miR-590-3p), CASC9, and the sine oculis homeobox 1 (SIX1) gene were determined through qRT-PCR. We conducted cell counting kit-8 (CCK-8) assays to assess cell proliferation, transwell assays to detect cell migration/invasion, and flow cytometry to evaluate cell apoptosis. StarBase v2.0 was used to predict interactions between miR-590-3p and SIX1 or CASC9, and dual-luciferase reporter assays were used to verify these predictions. CASC9 protein was overexpressed in BC cells and tissues, while CASC9 knockdown inhibited BC cell growth, invasion, and migration and promoted apoptosis. Additionally, we verified that CASC9 competes for binding with miR-590-3p. Moreover, SIX1 was determined to be a target of miR-590–3p, and SIX1 expression was inhibited by miR-590-3p overexpression. CASC9 enhanced BC development by downregulating miR-590-3p and upregulating SIX1 during the activation of the NF-κB pathway. These data suggest that the CASC9/miR-590-3p/SIX1/NF-κB axis is involved in breast cancer progression, providing insight into the function of CASC9 in breast cancer development.

LncRNA CASC9 activated by STAT3 promotes the invasion of breast cancer and the formation of lymphatic vessels by enhancing H3K27ac‐activated SOX4

“…CASC9 acted as a potential tumor‐promoting gene, and the clinical expression or phenotype was determined in BC tissues in our previous study. Additionally, CASC9 could promote the malignant behavior of BC cells via activation of NF‐κB signaling 13 . Similarly, our results revealed that CASC9 was markedly upregulated in BC and correlated with lymph node metastasis, tumor size, and advanced TNM stage.…”

“…25,26 For instance, Shi et al's study showed that lncRNA HANR silencing could decrease the hepatocellular carcinoma-associated invasion and lymphatic vessel formation abilities of HDLECs by targeting the miR-296/EAG1/VEGF axis. 25 13 Similarly, our results revealed that CASC9 was markedly upregulated in BC and correlated with lymph node metastasis, tumor size, and advanced TNM stage. By cellular biological role analysis, CASC9 silencing was shown to inhibit the proliferative and invasive abilities of BC cells and further decrease the BCassociated invasion and lymphatic vessel formation of HDLECs.…”

“…Moreover, it has been reported that upregulation of CASC9 was associated with TNM stage, overall survival rate, and lymphatic metastasis in liver cancer 11,12 . Previous studies also demonstrated that CASC9 could promote the proliferation and invasion of BC cells 13,14 . However, the underlying mechanism of CASC9 in lymphatic formation and metastasis of BC remains largely unknown.…”

“…11,12 Previous studies also demonstrated that CASC9 could promote the proliferation and invasion of BC cells. 13,14 However, the underlying mechanism of CASC9 in lymphatic formation and metastasis of BC remains largely unknown. SRY-box transcription factor 4 (SOX4), located on chromosome 6p22.3, belongs to the SOX transcription factor family, which plays vital roles in cell stemness, differentiation, progenitor development, and so on.…”

A high level of the long non-coding RNA MCF2L-AS1 is associated with poor prognosis in breast cancer and MCF2L-AS1 activates YAP transcriptional activity to enhance breast cancer proliferation and metastasis

“…Dysregulation of lncRNA expression patterns is now recognized as a prevalent finding in a variety of malignancies, with these ncRNAs having the ability to control oncogenic processes such as tumor cell motility, proliferation, survival, invasion, stemness, microenvironmental remodeling, and metastasis [ 42–44 ]. Several studies have examined the functions of lncRNAs in BC [ 9 , 10 , 31 ]. MCF2L-AS1 is a lncRNA that was recently identified and found to be dysregulated in multiple human cancer types in which it regulates progression-related disease processes [ 11 ].…”