Long Non-coding RNA SNHG17 Promotes Cell Proliferation and Invasion in Castration-Resistant Prostate Cancer by Targeting the miR-144/CD51 Axis

Abstract

Previously, we found that the expression of long non-coding RNA (lncRNA) small nucleolar RNA host gene 17 (SNHG17) was up-regulated in castration-resistant prostate cancer (CRPC) cells compared to that in hormone sensitive prostate cancer (HSPC) cells. Moreover, we found that CD51 was up-regulated in prostate cancer cells and promoted the carcinogenesis and progression of prostate cancer. However, the regulatory mechanism of SNHG17 and CD51 in the development of CRPC remains unclear. In the current study, we aimed to elucidate the expressions, functions, and underlying mechanism of SNHG17 and CD51 in CRPC. Our results further confirmed that both SNHG17 and CD51 were up-regulated in CRPC tissues and cells. In addition, we found that SNHG17 expression was positively correlated with CD51 expression in prostate cancer. Mechanically, SNHG17 functioned as a competing endogenous RNA (ceRNA) to up-regulate CD51 expression through competitively sponging microRNA-144 (miR-144), and CD51 was identified as a direct downstream target of miR-144 in CRPC. Functionally, down-regulation of SNHG17 or up-regulation of miR-144 inhibited the proliferation, migration, and invasion of CRPC cells, whereas up-regulation of SNHG17 and down-regulation of miR-144 promoted the proliferation, migration and invasion of CRPC cells in vitro and in vivo. Using gain and loss-of function assay and rescue assay, we showed that miR-144 inhibited cell proliferation, migration and invasion by directly inhibiting CD51 expression, and SNHG17 promoted cell proliferation, migration and invasion by directly enhancing CD51 expression in CRPC cells. Taken together, our study reveals the role of the SNHG17/miR-144/CD51 axis in accelerating CRPC cell proliferation and invasion, and suggests that SNHG17 may serve as a novel therapeutic target for CRPC.

Autophagy-related long non-coding RNA signature for ovarian cancer

“…24 Upregulation of SNHG17 promoted the proliferation, migration and invasion of prostate cancer cells in vitro and in vivo. 25 Another study found that LBX2-AS1, upregulated by NFIC, promoted gastric cancer progression via targeting miR-491-5p/zinc finger protein 703 (ZNF703). 26 Higher expression levels of LBX2-AS1 had unfavorable effects on patient OS and promoted activation of the Notch pathway.…”

Identification of Autophagy-Related Long Non-Coding RNA Prognostic Signature for Clear Cell Renal Cell Carcinoma

“…The EMT process induced by nuclear factor-κ B signaling pathway may be the potential mechanism [19]. Small nucleolar RNA host gene 17 (SNHG17) was reported to accelerate cell proliferation and invasion in castrationresistant prostate cancer (CRPC) by targeting the miR-144/CD51 axis [20]. Furthermore, as lncRNAs that encode small nucleolar RNAs (snoRNAs), the prognostic value of SNHG17 and SNHG15 in KIRC patients has been investigated, and DNA hypomethylation might play a key role in elevated SNHG15 transcription in KIRC [21].…”

MicroRNA-144: A novel biological marker and potential therapeutic target in human solid cancers

“…In addition, lncRNA small nucleolar RNA host gene 17 (SNHG17) functions as a ceRNA to up-regulate CD51 expression through competitively combining with miR-144 in CRPC. Up-regulation of CD51 is closely related to cancer progression and poor prognosis in multiple types of cancers [81]. In LSCC, the lncRNA X-Inactive Specific Transcript (XIST) promotes the tumor progression by sequestering miR-144 to regulate IRS1 expression [82].…”