Hypoxia-Induced Upregulation of lncRNA ELFN1-AS1 Promotes Colon Cancer Growth and Metastasis Through Targeting TRIM14 via Sponging miR-191-5p

Abstract

Hypoxia is identified as one of the microenvironmental features of most solid tumors and is involved in tumor progression. In the present research, we demonstrate that lncRNA extracellular leucine rich repeat and fibronectin type III domain-containing 1-antisense RNA 1 (ELFN1-AS1) is upregulated by hypoxia in colon cancer cells. Knockdown of ELFN1-AS1 in hypoxic colon cancer cells can reduce cell proliferation and restore the invasion to non-hypoxic levels. Fluorescence in situ hybridization results show that ELFN1-AS1 is distributed in the cytoplasm of colon cancer cells, so we further analyze the potential targets for ELFN1-AS1 as a competing endogenous RNA (ceRNA). MiR-191-5p contains a binding sequence with ELFN1-AS1 and is downregulated by ELFN1-AS1 in colon cancer cells. Then, there is a binding site between miR-191-5p and the 3′ untranslated region of tripartite motif TRIM 14 (TRIM14). The expression of TRIM14 is inhibited by ELFN1-AS1 siRNA or miR-191-5p mimics in LoVo and HT29 cells. The treatment of the miR-191-5p inhibitor in ELFN1-AS1 knockdown cells can significantly increase cell proliferation and invasion ability. Overexpression of TRIM14 in miR-191-5p-mimic-treated cells can rescue the inhibition of proliferation and invasion caused by miR-191-5p mimics. In conclusion, ELFN1-AS1 operates as a downstream target of hypoxia, promotes proliferation and invasion, and inhibits apoptosis through upregulating TRIM14 by sponging miR-191-5p in the colon cancer cells. Our results enrich our understanding of colon cancer progression and provide potential targets for clinical treatment of colon cancer.

Identification of Immune-Related lncRNAs for Predicting Prognosis and Immune Landscape Characteristics of Uveal Melanoma

“…We found that CD4+ T cells, CD8+ T cells, NK cells, M1 macrophages, M2 macrophages, myeloid dendritic cells, and fibroblasts were more abundant in the high-risk group. Significantly, high lymphocytic infiltration in um is associated with poor prognosis, in agreement with our results [ 23 – 29 ]. We also found that the expression of most ICIs-related molecules and the scores of most immune functions were higher in the high-risk group than low-risk group.…”

“…en, 409 irlncRNAs were associated with prognosis, 6 candidate irlncRNAs (ELFN1-AS1, AF131216.4, AP005121.1, AC079089.1, AC104117.3, and SOX1-OT) were filtered out by LASSO, and 3 prognostic irlncRNAs were applied to construct a model. Among these 6 candidate irlncRNAs, ELFN1-AS1 was considered as an oncogene in a variety of cancers, AC079089.1, AC104117.3, and SOX1-OT have been shown to have a function in the progression of various diseases, and other lncRNAs were first identified [23][24][25][26][27][28].…”

MiR-191-5p Attenuates Tau Phosphorylation, Aβ Generation, and Neuronal Cell Death by Regulating Death-Associated Protein Kinase 1

“…In addition to DAPK1, miR-191-5p has been found to target oxidative stress responsive 1 (OXSR1), 57 special AT-rich binding protein 1 (SATB1), 58 CCAAT-box/enhancer binding protein β (C/EBPβ), 59 mitogen-activated protein kinase kinase kinase 12 (Map3k12), 60 and tripartite motif-containing 14 (TRIM14). 61 These targets have similar sequences that bind to the short seed sequences at the 5′ ends (nucleotides 2−8) of miR-191-5p. Nevertheless, the regulatory roles of miR-191-5p through its downstream targets in AD remain to be further investigated and are worthy of more in-depth exploration in future studies.…”

TRIM family contribute to tumorigenesis, cancer development, and drug resistance

“…ROS can upregulate TRIM37 during HBV (Hepatitis B)-associated hepatic fibrosis which is a high risk factor for hepatocellular carcinoma [ 108 ]. Under a hypoxic conditions, TRIM14 was induced by sponging miR-191-5p in colon cancer cells, inhibiting apoptosis and promoting proliferation and invasion [ 109 ]. Some TRIMs may play opposite roles: TRIM4 could sensitize cells to hydrogen peroxide (H 2 O 2 ) induced cell death [ 110 ].…”