N6-methyladenine- induced LINC00667 promoted breast cancer progression through m6A/KIAA1429 positive feedback loop

Abstract

Increasing evidence supports that N 6 -methyladenine (m 6 A) and long noncoding RNAs (lncRNAs) both act as master regulators involved in breast cancer (BC) tumorigenesis at epigenetic modification level. Here, our research tries to unveil the interaction of m 6 A and lncRNAs on BC progression and explore the underlying regulatory mechanism. In the current study, we found that LINC00667 was m 6 A-modified lncRNA, which was up-regulated upon the overexpression of KIAA1429. The high expression of LINC00667 was correlated with the prognosis of BC patients. Bio-functional assays indicated that LINC00667 promoted the proliferation and migration of BC cells. Mechanistic assays illustrated that KIAA1429 targeted the m 6 A modification site of LINC00667 and enhanced its mRNA stability. Moreover, LINC00667 positively regulated the KIAA1429 via sponging miR-556-5p, forming a KIAA1429/m 6 A/LINC00667/miR-556-5p feedback loop. Collectively, the central findings of our study suggest that KIAA1429-induced LINC00667 exerted its functions as an oncogene in BC progression through m 6 A-dependent feedback loop.

Unraveling the cross‐talk between N6‐methyladenosine modification and non‐coding RNAs in breast cancer: Mechanisms and clinical implications

“…KIAA1429 targets the m6A modification site of LINC00667 and increases its mRNA stability, forming a KIAA1429/m6A/LINC00667/miR-556-5p feedback circuit that accelerates BC progression. 43 Furthermore, bioinformatics analysis combined with RIP and Methylation-specific PCR (MSP) assays indicated that in BC cell lines (MCF-7, T47D, and MDA-MB-231), the highly expressed LncRNA urothelial carcinoma-associated 1(UCA1) recruited DNA methyltransferases to the METTL14 promoter region, thereby inhibiting the expression of METTL14. the down-regulated METTL14 suppressed the m6A modification of miR-375, which altered the expression of the downstream target SOX12.…”

“…LINC00667 functions as a sponge for miR-556-5p and positively regulates KIAA1429, resulting in a regenerative feedback loop of KIAA1429/m6A/LINC00667/ miR-556-5p that promotes BC progression. 43 In SKBR3 cells, VIRMA upregulates m6A-modified lncRNA NEAT1, which accelerates BC cell proliferation. 73 In contrast, certain lncRNAs regulated by m6A…”

“…Similarly, Luciferase reporter assay and RIP assay demonstrated that LINC00667 sponge adsorbed miR‐556‐5p in BC cells (MDA‐MB‐231, MCF‐7) and positively regulates KIAA1429. KIAA1429 targets the m6A modification site of LINC00667 and increases its mRNA stability, forming a KIAA1429/m6A/LINC00667/miR‐556‐5p feedback circuit that accelerates BC progression 43 . Furthermore, bioinformatics analysis combined with RIP and Methylation‐specific PCR (MSP) assays indicated that in BC cell lines (MCF‐7, T47D, and MDA‐MB‐231), the highly expressed LncRNA urothelial carcinoma‐associated 1(UCA1) recruited DNA methyltransferases to the METTL14 promoter region, thereby inhibiting the expression of METTL14.…”

“…In both MDA‐MB‐231 and MCF‐7 cells, KIAA1429 targets the m6A modification site of LINC00667 to enhance its mRNA stability. LINC00667 functions as a sponge for miR‐556‐5p and positively regulates KIAA1429, resulting in a regenerative feedback loop of KIAA1429/m6A/LINC00667/miR‐556‐5p that promotes BC progression 43 . In SKBR3 cells, VIRMA upregulates m6A‐modified lncRNA NEAT1, which accelerates BC cell proliferation 73 .…”

Epitranscriptomic orchestrations: Unveiling the regulatory paradigm of m6A, A‐to‐I editing, and m5C in breast cancer via long noncoding RNAs and microRNAs

“…108 Lastly, m6A-induced LINC00667 promotes BC progression by a positive feedback loop involving m6A and KIAA1429. 133 In 2004, Luciano and colleagues provided the inaugural evidence of miRNA editing, reporting A-to-I conversion within the miR-22…”