X chromosome‐linked long noncoding RNA lnc‐XLEC1 regulates c‐Myc‐dependent cell growth by collaborating with MBP‐1 in endometrial cancer

Abstract

LncRNAs (long noncoding RNAs) are noncoding transcripts that are more than 200 nt long and have been described as the largest subclass in the noncoding transcriptome in humans. Although studies of lncRNAs in cancer have been continuing for a long time, no much has been known about X chromosome‐linked lncRNAs. Here, by using RNA‐seq we report the identification of a new X chromosome‐linked lncRNA (lnc‐XLEC1) that is aberrantly downregulated during the development of endometrial carcinoma (EC). The overexpression of lnc‐XLEC1 reduces the migration and proliferation of EC cells. Flow cytometry analysis indicated that lnc‐XLEC1 overexpression resulted in a substantial accumulation of EC cells in the G1 phase. In addition, lnc‐XLEC1 had inhibitive effects that may result from its collaboration with MBP‐1 during the suppression of the c‐Myc expression and the negative regulating of the Cdk/Rb/E2F pathway. The anti‐tumor effects of lnc‐XLEC1 on EC progression suggest that lnc‐XLEC1 has some potential value in anti‐carcinoma therapies and deserves further investigation. Our study reported for the first time that the lnc‐XLEC1 might be related to the incidence and prognosis of EC. Moreover, we discovered that this process might be related to somatic X dosage compensation and skewed X chromosome inactivation (SXCI).

<p>LINC00958-MYC positive feedback loop modulates resistance of head and neck squamous cell carcinoma cells to chemo- and radiotherapy in vitro</p>

“…Furthermore, c-Myc, as a transcription factor, is a proto-oncogene and in human cancers, c-Myc is frequently constitutively expressed, which results in enhanced expression of various cell growth-related and apoptosis-resistant genes to promote carcinogenesis 32. Previous studies showed that a remarkable association of aberrant lncRNA expression with c-Myc 7,28,33–35. These publications demonstrated that c-Myc promoted normal cells to neoplastic transformation by affecting a drastic change in the number and the type of gene expression, including various lncRNAs in different human cancers 28.…”

“…And lncRNA can bind to chromatin modifying factors or other transcriptional factors 18,25. Previous studies revealed that different lncRNAs are able to directly bind to c-Myc and affect c-Myc transcriptional activity 7,28,33,34. For instance, lncRNA MINCR was shown to bind and affect c-Myc transcriptional activity by recruiting an MYC co-activator to c-Myc-targeted gene promoters for activation of their transcription in cells,39 while lncRNA PDIA3P26 and PCGEM140 showed to bind to c-Myc to induce gene expression.…”

RETRACTED: LINC00461 Promoted Endometrial Carcinoma Growth and Migration by Targeting MicroRNA-219-5p/Cyclooxygenase-2 Signaling Axis

“…lncRNAs are reported to be involved in a range of developmental processes and diseases, especially human cancers 7 . Several lncRNAs, such as lncRNA lnc-XLEC1, lncRNA LINC00672, and lncRNA HAND2-AS1, have been identified in EC pathogenesis [8][9][10] . Located at an intergenic region between two protein-coding genes (myocyte enhancer factor 2C and transmembrane protein 161B), LINC00461 is reported to be dysregulated in several types of cancers.…”

Endometrial Cancer Stem Cells: Where Do We Stand and Where Should We Go?

“…This inactivation led to reduced c-Myc expression as well as Snail and N-cadherin and the overexpression of PI3K in α-Enolase silenced endometrial cancer cells reversed this effect [ 82 ]. However, c-Myc promoter binding protein 1 (MBP-1), an alternative translation product of α-Enolase, has been shown to suppress c-Myc expression, which reduced the proliferation and migration of endometrial cells [ 83 ]. Targeting the Hedgehog signaling pathway, which has been suggested to maintain CSCs [ 84 ], significantly inhibited the growth of endometrial cancer cells with a concomitant reduced expression of cyclin D1 and N-Myc [ 85 ].…”