DLX6-AS1: A Long Non-coding RNA With Oncogenic Features.

Soudeh Ghafouri-Fard,Sajad Najafi,Bashdar Mahmud Hussen,Aryan R Ganjo,Mohammad Taheri,Mohammad Samadian

doi:10.3389/fcell.2022.746443

Abstract

Long non-coding RNAs (lncRNAs) are a heterogeneous group of ncRNAs with characteristic size of more than 200 nucleotides. An increasing number of lncRNAs have been found to be dysregulated in many human diseases particularly cancer. However, their role in carcinogenesis is not precisely understood. DLX6-AS1 is an lncRNAs which has been unveiled to be up-regulated in various number of cancers. In different cell studies, DLX6-AS1 has shown oncogenic role via promoting oncogenic phenotype of cancer cell lines. Increase in tumor cell proliferation, migration, invasion, and EMT while suppressing apoptosis in cancer cells are the effects of DLX6-AS1 in development and progression of cancer. In the majority of cell experiment, mediator miRNAs have been identified which are sponged and negatively regulated by DLX6-AS1, and they in turn regulate expression of a number of transcription factors, eventually affecting signaling pathways involved in carcinogenesis. These pathways form axes through which DLX6-AS1 promotes carcinogenicity of cancer cells. Xenograft animal studies, also have confirmed enhancing effect of DLX6-AS1 on tumor growth and metastasis. Clinical evaluations in cancerous patients have also shown increased expression of DLX6-AS1 in tumor tissues compared to healthy tissues. High DLX6-AS1 expression has shown positive association with advanced clinicopathological features in cancerous patients. Survival analyses have demonstrated correlation between high DLX6-AS1 expression and shorter survival. In cox regression analysis, DLX6-AS1 has been found as an independent prognostic factor for patients with various types of cancer.

Highlights

In complex organisms, genome sequencing analyses have unveiled that just a small fraction of genome (e.g., 1–2% for mammals) encodes for protein via coding RNAs or messenger RNAs that are located in the middle of central dogma making connection between DNA and corresponding protein
LncRNAs are a heterogeneous group of ncRNAs with characteristic size of more than 200 nucleotides
An increasing number of long ncRNAs (lncRNAs) have been found to be dysregulated in many human diseases cancer

Summary

INTRODUCTION

Genome sequencing analyses have unveiled that just a small fraction of genome (e.g., 1–2% for mammals) encodes for protein via coding RNAs or messenger RNAs (mRNAs) that are located in the middle of central dogma making connection between DNA and corresponding protein. Examples of these databases are TRlnc for regulatory lncRNAs in humans (Li et al, 2020a), lncRNASNP1 and 2 for single nucleotide polymorphisms (SNPs) of human and mouse lncRNAs (Gong et al, 2014; Miao et al, 2017), LncRNA2Target v2.0 for target genes of lncRNAs (Cheng et al, 2018), CRISPRlnc for validated single guide RNAs (sgRNAs) used in clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein number 9 (Cas9) gene editing technology for lncRNAs (Chen et al, 2018) and clusLnc2Cancer for effective lncRNAs in human cancers (Ning et al, 2015) They act in cis and trans modes by gathering and localizing transcription factors to a locus. DLX6-AS1 gene is located on chromosome 7q21.3, primarily identified by Feng et al (2006) to promote DLX5/6 function in trans mode This lncRNA has been found to be up-regulated in a growing number of different types of cancerous tissues compared to normal tissues.

Female nude mice

Multivariate cox regression

Kong and matched NATs

Findings

DISCUSSION