<p>Long noncoding RNA LINC01089 predicts clinical prognosis and inhibits cell proliferation and invasion through the Wnt/β-catenin signaling pathway in breast cancer</p>

Abstract

Background Recently, emerging evidence has indicated crucial roles for long noncoding RNAs (lncRNAs) in breast cancer (BC) development and progression. Our study aimed to investigate the clinical significance of LINC01089 in patients with BC and to determine its biological functions and underlying molecular mechanisms. Materials and methods Correlations between LINC01089 expression and the clinicopathological characteristics of BC patients were assessed using chi-square tests. The Kaplan-Meier method was used to produce survival curves. The clinical risk characteristics associated with the overall survival and recurrence-free survival of patients with BC were estimated using univariate and multivariate Cox regression analyses. Several methods were used to determine the expression profile, biological functions and underlying mechanisms of LINC01089 in BC, including cell proliferation assays, colony formation assays, flow cytometry, transwell assays, wound healing assays, quantitative real-time polymerase chain reaction and Western blotting. Results LINC01089 was downregulated in BC tissues and cell lines. Low LINC01089 expression was significantly correlated with age ( P =0.026), lymph node metastasis ( P =0.003), and poor prognosis of patients with BC. According to the multivariate Cox regression analysis results, LINC01089 was an independent prognostic indicator of overall survival ( P =0.032) and recurrence-free survival ( P =0.014). Functional studies revealed significant decreases in the proliferation, migration, and invasion of tumor cells overexpressing LINC01089, and EGF could reverse above effects of LINC01089 on BC cells. Additionally, increased LINC01089 expression promoted apoptosis and cell cycle arrest at G0/G1 phase, accompanied by decreased expression of the key cell cycle regulators CDK4 and CDK6. Loss-of-function assays confirmed partial results. Mechanistically, LINC01089 blocked the Wnt/β-catenin pathway and the expression of downstream target genes by inhibiting β-catenin expression at the transcriptional level. Conclusion Based on our results, LINC01089 functions as a tumor suppressor and potentially represents a novel prognostic indicator and therapeutic target in BC.

An in-silico method leads to recognition of hub genes and crucial pathways in survival of patients with breast cancer

“…Yuan et al have reported a significant correlation between low expression of LINC01089 and lymph node metastasis and poor prognosis of breast cancer. LINC01089 is modulates breast tumorigenesis by inhibiting β-catenin transcription and consequently blocking Wnt/β-catenin signaling 51 . LINC02256 (ENSG00000261064) is a validated novel long intergenic non-protein coding RNA with 2 transcripts which is located on 15q13.3.…”

<p>LINC01089 Blocks the Proliferation and Metastasis of Colorectal Cancer Cells via Regulating miR-27b-3p/HOXA10 Axis</p>

“…In breast cancer, LINC01089 overexpression impedes cancer metastasis via regulating Wnt/ β-catenin signaling. 24 Moreover, LINC01089 is downregulated in glioma tissues, and its down-regulation predicts unfavorable prognosis of the patients; additionally, and its restoration impedes the malignant biological behaviors of glioma cells. 25 Nevertheless, previously, the function and underlying mechanism of LINC01089 during CRC progression had not been clarified.…”

“…These data indicated that LINC01089 played a tumor suppressive role in CRC, which is similar with its function in other cancers. [23][24][25] LncRNA can share miRNA response elements of mRNA and competitively bind with miRNAs to reduce its availability, functioning as competitive endogenous Figure 5 The function of LINC01089 in CRC cells was dependent on miR-27b-3p/HOXA10 axis. (A) MiR-27b-3p mimics were transfected in SW620 and LoVo cells with LINC01089 overexpression.…”

Managing therapeutic resistance in breast cancer: from the lncRNAs perspective

“…These findings indicate that Lnc712 may enhance resistance to palbociclib and become a promising biomarker for the prediction of drug response in BC. Similarly, lncRNAs associated with other CDKs, including MALAT1 104 , TUG1 105 , CCAT2 106 and LINC01089 107 , may also mediate resistance to CDK inhibitors. Overall, the direct nexus between lncRNAs and CDK inhibitors is not yet well established.…”