Kunnathur Murugesan Sakthivel (2025) Long non-coding RNA Nkx2-2as/BTG2 axis attenuates breast cancer progression by targeting Wnt/β-catenin signaling. Long non-coding RNA Nkx2-2as/BTG2 axis attenuates breast cancer progression by targeting Wnt/β-catenin signaling, 43: 12. pp. 1-25.

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Abstract

Breast cancer (BC) is the second leading cause of cancer-related deaths among women, primarily due to late-stage detec�tion and therapy resistance. Therefore, identifying novel therapeutic targets is critical for improving BC outcomes. Long
non-coding RNAs (lncRNAs) have recently emerged as promising candidates for cancer prognosis and treatment, owing
to their ability to modulate oncogenic signaling pathways. Among them, the tumor-suppressive lncRNA Nkx2-2as has
shown inhibitory effects in certain cancers; however, its role in BC remains poorly understood. To the best of our cur�rent knowledge, the relationship between Nkx2-2as and the Wnt/β-catenin signaling pathway in BC has not been previ�ously characterized. To address this, we used computational tools including lncHUB2, RPISeq, GeneMANIA, TCGA and
ENCORI to predict functional interactions of Nkx2-2as, which guided our focus toward its involvement in the Wnt/β�catenin signaling pathway, a key driver in BC progression. We hypothesized that Nkx2-2as may act as a pharmacologically
actionable molecule in this context. To test this, MCF-7 breast cancer cells were transfected with either Nkx2-2as siRNA
or an Nkx2-2as-pcDNA3.1 overexpression vector, individually and in combination. Overexpression of Nkx2-2as led to
a significant reduction in proliferation (~85%), suppression of migration, and increased apoptosis. Conversely, silencing
Nkx2-2as enhanced tumorigenic properties. Mechanistic analyses revealed that Nkx2-2as downregulates oncogenic targets
such as β-catenin, TCF7 and MYC, while upregulating tumor suppressors AXIN2 and BTG2, the latter being a known
inhibitor of β-catenin. Western blot analysis confirmed the transcriptional trends, showing decreased β-catenin and MYC
and elevated BTG2 protein levels upon Nkx2-2as overexpression. These findings indicate that Nkx2-2as acts as a nega�tive regulator of Wnt/β-catenin signaling through BTG2 activation, suggesting its potential role as a tumor suppressor and
a candidate for RNA-based therapeutic strategies in BC. Targeting the Nkx2-2as/BTG2 axis may provide a conceptual
framework for future studies aimed at developing RNA-based interventions to enhance chemosensitivity and overcome
therapy resistance in BC

Item Type: Article
Uncontrolled Keywords: Breast cancer · LncRNA · Nkx2-2as · Wnt/β-catenin signalling · BTG2 · RNA based therapy
Divisions: PSG College of Arts and Science > Department of Biochemistry
Depositing User: Dr. B Sivakumar
Date Deposited: 06 Mar 2026 08:24
Last Modified: 06 Mar 2026 08:24
URI: https://ir.psgcas.ac.in/id/eprint/2685

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