LncRNA MONC suppresses the malignant phenotype of Endometrial Cancer Stem Cells and Endometrial Carcinoma Cells by regulating the MiR-636/GLCE axis

Abstract

Background Emerging evidence shows that abnormal expression of long non-coding RNA is involved in the occurrence and development of various tumors. LncRNA MONC is abnormally expressed in head and neck squamous cell carcinoma, lung cancer, colorectal cancer, and acute megakaryocytic leukemia, but the biological function and potential regulatory mechanism of MONC in endometrial cancer stem cells (ECSCs) and endometrial cancer cells (ECCs) have not been studied. In this study, we aimed to explore the tumor suppressive effect and mechanism of MONC in regulating ECSCs and ECCs. Methods We used qRT-PCR to detect the expression of MONC, miR-636 and GLCE in normal human endometrial tissues and endometrial carcinoma (EC) tissues. Luciferase assay was used to verify the binding sites between MONC and miR-636 and between miR-636 and GLCE. Double fluorescence in situ hybridization was used to locate MONC and miR-636 in cells. ECSCs were obtained by flow cytometry sorting assay. Sphere formation assay, CCK-8 assay, transwell invasion assay, cell cycle analysis and apoptosis assay were used to detect the effects of MONC/miR-636/GLCE axis on the malignant biological behavior of ECSCs and ECCs. The effect of MONC on the epithelial-to-mesenchymal transition (EMT) process was detected using western blot. Finally, we conducted in vivo verification through Tumor xenografts in BALB/C nude mice. Results In this study, we found MONC is low expression in endometrial carcinoma (EC) and patients in the MONC high-expression group had a better prognosis. MONC and miR-636 are relatively co-localized in the cytoplasm. MONC directly inhibits the malignant biological behavior of ECSCs and ECCs by directly inhibiting miR-636. Simultaneously, miR-636 may indirectly reduce the expression of MONC. Down-regulation of miR-636 may promote GLCE expression by targeting the 3′-untranslated region (UTR) of the downstream gene GLCE, thereby inhibiting the progression of ECSCs. MONC combined with miR-636 inhibited tumor epithelial-to-mesenchymal transition (EMT) process. In addition, we verified the tumor suppressive effect of MONC in nude mice, miR-636 can rescue the tumor suppressive effect of overexpressing MONC. Conclusions In conclusion, this study showed that MONC inhibits the malignant phenotypes of ECSCs and ECCs by regulating the miR-636/GLCE axis. Thus the MONC/miR-636/GLCE axis may provide novel treatment avenues for human EC.

lncRNA NBAT1 Inhibits Cell Metastasis and Promotes Apoptosis in Endometrial Cancer by Sponging miR-21-5p to Regulate PTEN

“…Recently, increasing evidence indicated that lnc-RNAs were implicated in the formation and development of EC. For example, Li et al [ 15 ] demonstrated that lnc-MONC restrains the grade malignancy of endometrial cancer stem cells (ECSCs) and endometrial cancer cells (ECCs) by ordering the miR-636/GLCE axis. Similarly, lncRNA HOXB-AS3 was upregulated in endometrial cancer tissues and cell lines, enhanced cell proliferation, and inhibited apoptosis in EC cells [ 16 ].…”

TGF-β-induced MIR99AHG synergizes with PTBP1 to trigger a splicing switch of SMARCA1 that promotes invadopodia formation for metastasis in colorectal cancer

“…We and others have revealed that MIR99AHG can act as an oncogene in myeloid leukaemia and gastric cancer 45,46 . Nevertheless, it was also reported as a tumor suppressor in lung adenocarcinoma and endometrial carcinoma 47,48 , highlighting the functional complexity and tumor specificity of MIR99AHG. In the present study, we found that MIR99AHG is upregulated in CRC cell lines, especially in those with a high metastatic potential.…”

Identification of Novel miRNAs, Targeting Genes, Signaling Pathway, and the Small Molecule for Overcoming Oxaliplatin Resistance of Metastatic Colorectal Cancer

“…Another example is bta-miR-26a which also reduced the abundance of PCK1 [44,45]. Moreover, the oncosuppressor miR-20a-3p was identified in melanoma, tongue squamous cell carcinoma, and hepatocellular carcinoma, and the oncosuppressor miR-636 was also identified in lung cancer, nasopharyngeal carcinoma, cervical cancer, endometrial cancer, ovarian cancer, and hepatocellular carcinoma [46][47][48][49][50][51][52][53][54][55][56]. It was reported that high miR-20a-3p and miR-636 expression were correlated with poor OS of CRC patients and this was consistent with our results.…”