LncRNA SNHG6 role in clinicopathological parameters in cancers

Abstract

RNA sequencing has revealed that a substantial portion of the human genome undergoes transcription, yet a minimal fraction of these transcripts translates into proteins. LncRNAs, RNA molecules less than 200 nt in length, once deemed as transcriptional noise, have now emerged as crucial regulators of numerous cellular processes. This review focuses on the lncRNA SNHG6, aiming to elucidate its biogenesis, the pivotal roles it plays, and its mechanisms in facilitating the hallmarks of cancer. A comprehensive literature review and analysis were undertaken to delve into the biogenesis of SNHG6, its roles in cellular processes, and the mechanisms through which it contributes to the hallmarks of cancer. SNHG6 is a notable lncRNA, observed to be overexpressed in various cancer types; its perturbation has been linked to tumor progression, emphasizing its significance in oncogenesis. This lncRNA contributes to a range of cellular aberrations, influencing transcriptional, post-transcriptional, and epigenetic processes of mRNA, ultimately driving cancerous transformations. LncRNA SNHG6 serves as a potential biomarker and therapeutic target due to its association with tumorigenesis. Understanding its mechanism and role in cancer can pave the way for novel diagnostic and therapeutic strategies.

Keywords: Cancer; Epigenetic control; LncRNA; Neoplastic gene regulation; Oncogenes; SNHG6; Signal transduction.

Fig. 1

Biogenesis of LncRNA. This figure illustrates the multi-step process of long non-coding RNA (LncRNA) biogenesis; starting from the genomic DNA, the process is initiated with the transcription of LncRNA genes by RNA polymerase, similar to protein-coding genes. Once transcribed, these primary LncRNA transcripts undergo various modifications: LncRNAs receive a 5' cap which helps in stabilization and prevention of degradation; intronic regions are removed, and exons are joined together; not all LncRNAs are spliced, and some exist as single exonic molecules. A poly-A tail is added at the 3' end of the RNA molecule, some LncRNAs are non-polyadenylated and hence lack this tail; while many LncRNAs function within the nucleus, some are exported to the cytoplasm, employing mechanisms similar to mRNAs; depending on their sequence and structure, LncRNAs interact with various cellular molecules such as DNA, RNA, or proteins to exert their functional roles

Fig. 2

SNHG6 mediated regulation of autophagy. Autophagy can be initiated by the activation of the UKL1 complex. The regulatory RNAs, i.e., miR-26a-5p and miR186 act as an antagonist and inhibit the activations of the UKL1 complex thus shutting down the autophagy. SNHG6 inhibits these regulatory miRNAs and makes UKL1 available to a cell which leads to the ATF3 and UKL1 complex activation and autophagosome formation that helps in cell survival. Activating transcription factor 3 (ATF3); autophagy-related protein 13 (ATG13); autophagy-related protein 101 (ATG101); microRNA-186 (miR-186); small nucleolar RNA host gene 6 (SNHG6); unc-51-like kinase 1 (ULK1); focal adhesion kinase family interacting protein of 200 kDa (FIP200)

Fig. 3

Diagram regarding the role of SNHG6 in the regulation of hallmarks of cancer. SNHG6 interacts with different miRNAs and activates the downstream signaling pathways;  this results in the perturbation in the signaling cascade resulting in uncontrolled cell differentiation, proliferation, tumorigenesis, inhibition of apoptosis, increase migration and metastasis. ↑increase, ↓decrease; enhancer of zeste homolog 2 (EZH2), nuclear cap-binding subunit 3 (NCBP3), LIM domain only 3 (LMO3), flotillin-1 (FLOT1), homeobox protein GBX-2 (GBX2), histone 3 lysine 27 trimethylation (H3K27me3), matrix metalloproteinases (MMP), mitogen-activated protein kinase 6 (MAPK6), vasodilator-stimulated phosphoprotein (VASP), laminin subunit gamma-1 (LAMC1), small nucleolar RNA host gene 6 (SNHG6)