DLX6‐AS1 accelerates cell proliferation through regulating miR‐497‐5p/SNCG pathway in prostate cancer

Abstract

Prostate cancer (PCa) has become the second leading cause of cancer‐related mortality in males worldwide. Although the long noncoding RNA DLX6‐AS1 has been recognized to be an oncogene in multiple cancers, the biological function and regulatory mechanism of DLX6‐AS1 in prostate cancer are still obscure. In the present study, we observed that DLX6‐AS1 was significantly upregulated in PCa tissues and cells. Knockdown of DLX6‐AS1 inhibited PCa progression by suppressing cell proliferation and accelerating cell apoptosis. Molecular mechanism exploration indicated that DLX6‐AS1 acted as a sponge for miR‐497‐5p and synuclein gamma (SNCG) was a downstream target gene of miR‐497‐5p. In addition, there was a negative correlation between DLX6‐AS1 and miR‐497‐5p in PCa tissues. Rescue assays showed that SNCG overexpression could partially recover DLX6‐AS1 knockdown‐mediated inhibition of progression in PCa. Furthermore, xenograft tumor model was established to determine the role of DLX6‐AS1 in PCa tumor growth and the results suggested that DLX6‐AS1 could facilitate tumor growth by regulating SNCG in vivo. In conclusion, our study investigated the biological function and underlying mechanism of DLX6‐AS1 in PCa and validated that DLX6‐AS1 functioned as an oncogene through miR‐497‐5p/SNCG axis.

DLX6-AS1: a putative lncRNA candidate in multiple human cancers

“…Recent studies confirmed that DLX6-AS1 is highly expressed in prostate cancer tissues and cells and has an important role in the progression of prostate cancer (Refs 69, 70). It was found that DLX6-AS1 recruits DNA methyltransferase 1 (DNMT1) to like-acetylglucosaminyltransferase (LARGE) promoter and induces the methylation of LARGE promoter to down-regulate the expression of LARGE, which finally enhances the proliferation, invasion, and metastasis of prostate cancer cells (Ref.…”

“…It was also identified that lncRNA DLX6-AS1 acts as a ceRNA of miR-497-5p and promotes the proliferation of prostate cancer cells and tumours through modulating the downstream target gene of miR-497-5p, synuclein gamma (SNCG), in vitro and in vivo (Ref. 70).…”

“…DLX6-AS1 acts as a ceRNA for miR-513c in HCC and NB (Refs 58, 74). In addition, DLX6-AS1 promotes the progression of pancreatic cancer, prostate cancer, and NB by sponging miR-497-5p (Refs 56, 66, 70). Moreover, DLX6-AS1 binds to and inhibits miR-195-5p in the bladder and ovarian cancer, leading to tumorigenesis (Refs 63, 73).…”

Strategies of LncRNA DLX6-AS1 on Study and Therapeutics

“…LncRNA DLX6-AS1 plays key regulatory roles in regulating tumorigenesis and progress via many mechanisms. One of the most important mechanisms is formation of lncRNA DLX6-AS1-miRNAs-mRNAs ceRNAs regulatory networks, in which lncRNA DLX6-AS1 serves as an endogenous competing RNA to competitively sponge miRNAs to further up-regulate the downstream target genes (mRNAs) of miRNAs ( Zeng et al, 2017 ; Zhang et al, 2017 ; An et al, 2018 ; Zhangmou et al, 2018 ; Li X. et al, 2019 ; Yang Q. et al, 2019 ; Zhang H. Y. et al, 2019 ; Li D. et al, 2019 ; Yang J. et al, 2019 ; Zhang N. et al, 2019 ; Fang et al, 2019 ; Huang et al, 2019 ; Lei et al, 2019 ; Sun et al, 2019 ; Wang et al, 2019 ; Zhao et al, 2019 ; Liu Y. et al, 2020 ; Du et al, 2020 ; Hu et al, 2020 ; Jia et al, 2020 ; Kong et al, 2020 ; Kong and Zhang, 2020 ; Liang et al, 2020 ; Qian et al, 2020 ; Wang et al, 2020 ; Xie et al, 2020 ; Yang et al, 2020 ; Liu et al, 2021 ; Wang et al, 2021 ; Wu et al, 2021 ; Zhao et al, 2021 ; Zheng et al, 2021 ; Zhu et al, 2021 ). Xue et al (2021) and Feng et al (2021) also reviewed the regulatory roles serving as a ceRNA in various tumors which influence the prognosis of patients and which may be the therapeutic and prognosis target in malignant tumors.…”

LncRNA RHPN1‐AS1 inhibition induces autophagy and apoptosis in prostate cancer cells via the miR‐7‐5p/EGFR/PI3K/AKT/mTOR signaling pathway

“…8 To date, several lncRNAs have been defined as PCa specific. 9 Nevertheless, investigation of the function and mechanism of novel lncRNAs is necessary to find functional biomarkers in PCa progression. RHPN1-AS1 is a lncRNA that was differentially expressed in PCa patients and the potential function of RHPN1-AS1 in multiple tumor progression has been reported.…”