Reduced lncRNA Aim enhances the malignant invasion of triple-negative breast cancer cells mainly by activating Wnt/β-catenin/mTOR/PI3K signaling.

Increasing evidence has suggested the important role of IncRNAs in the progression of triple-negative breast cancer (TNBC). In the current study, we first demonstrated that the expression of Airn was reduced in TNBC tissues and cells. Our data showed that the level of Airn was reduced in TNBC tissues and cell lines compared with that of normal control. Furthermore, silencing of Aim markedly enhanced MDA-MB-231 cell migration. Meanwhile, knockdown of Airn significantly increased MDA-MB-231 cell invasion. Western blot analysis showed that knockdown of Airn markedly enhanced the activation of Wnt/beta-catenin/mTOR/PI3K in both MDA-MB-231 cells. Moreover, real time PCR analysis showed that the mRNA level of IGF2R was significantly enhanced when Airn was silenced in MDA-MB-231 cells. In addition, overexpression of IGF2R significantly increased MDA-MB-231 cell migration and invasion. To further explore whether Airn activated Wnt/beta-catenin/mTOR/PI3K signaling independent of IGF-2R, a specific siRNA targeting IGF2R was selected. Western blot analysis showed that Wnt/beta-catenin/mTOR/PI3K signaling could be largely activated in MDA-MB-231 cells transfected with siRNA targeting Airn, even when the protein level of IGF2R was silenced. In summary, decreased expression of IncRNA Aim enhanced the malignant invasion of triple-negative breast cancer cells mainly by activating Wnt/beta-catenin/mTOR/PI3K signaling independent of Igf2R.