ALDH1A3–Linc00284 Axis Mediates the Invasion of Colorectal Cancer by Targeting TGFβ Signaling via Sponging miR-361-5p

Abstract

ALDH1A3 and Linc00284 involve in colorectal cancer (CRC) development; however, the regulatory mechanism is still unclear. In this study, we collected clinicopathological characteristics and tissue samples from 73 CRC patients to analyze the expression of ALDH1A3, Linc00284, TGFβ signaling and miR-361-5p using qPCR, Western blotting, and ELISA. Multiple CRC cell lines were evaluated in this study, and the highest level of ALDH1A3 was observed in SW480 cells. To investigate the regulatory mechanism, RIP and luciferase assays were used to validate the interaction between Linc00284, miR-361-5p, and TGFβ. Proliferation, viability, migration, and invasion assays were performed to profile the effects of the ALDH1A3–Linc00284 axis in CRC cell functions, which was upregulated in CRC tissues. Knockdown ALDH1A3 or Linc00284 significantly reduced TGFβ expression and suppressed the EMT process, while overexpression had opposite effects. miR-361-5p targeted TGFβ directly, which negatively correlated with ALDH1A3–Linc00284 expression and CRC progression. Mechanistically, upregulation of ALDH1A3–Linc00284 promotes colorectal cancer invasion and migration by regulating miR-361-5p/TGFβ signaling pathway. Dysregulation of the ALDH1A3–Linc00284-miR-361-5p-TGFβ axis causes CRC invasion, which might provide a new insight into the treatment of CRC.

Study on the mechanism of miR-361-5p regulation of androgen receptor in castration-resistant transformation of prostate cancer

“…The level of miRNAs in tumor cells is different from that of healthy cells, and their up-regulated or downregulated expression plays a key role in the activation of gene signaling pathways in cancer development [10]. Among them, dysregulation of miR-361-5p plays an important role in human cancers and its abnormal expression has been found in human lung, breast, colorectal, cervical, ovarian, gastric, and retinoblastoma cancers [11][12][13][14][15][16][17] and exists as a pro-or oncogenic factor. Our functional experiments demonstrated that miR-361-5p inhibited the proliferation and migration of LNCAP cells and promoted their apoptosis.…”

ALDH1A3 promotes invasion and metastasis in triple‐negative breast cancer by regulating the plasminogen activation pathway

“…This reveals the dependence on other factors, which may be cell line or patient tumour‐specific factors that may be less commonly expressed. For example, it has been previously described that ALDH1A3 regulates gene expression via microRNAs [ 47 ], long non‐coding RNAs [ 52 , 53 , 54 , 55 , 56 , 57 ], and activation of the phosphatidylinositol 3‐kinase/Protein kinase B/rapamycin (PI3K/AKT/mTOR) signalling pathway [ 58 ]. It is possible that these ALDH1A3‐regulated factors are contributing to the regulation of PLAU and SERPINB2 by ALDH1A3 and ATRA does not fully replicate the cell signalling events induced by ALDH1A3.…”