lncRNA HCP5 acts as a ceRNA to regulate EZH2 by sponging miR‑138‑5p in cutaneous squamous cell carcinoma

Abstract

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are essential for the progression of tumors, including cutaneous squamous cell carcinoma (CSCC). The present study aimed to examine the competing endogenous RNA (ceRNA) network in CSCC. Differentially expressed genes in CSCC were analyzed using the GSE66359 microarray data set, and the upstream miRNAs and lncRNAs were predicted using online database analysis (TargetScan 7.1, mirDIP 4.1, miRSearch V3.0, miRDB and RNA22 2.0) and were verified in clinical tissues. RNA pull-down and dual luciferase reporter gene assays were used to verify the targeting relationships among lncRNA human histocompatibility leukocyte antigen complex P5 (HCP5), miR-138-5p and enhancer of zeste homolog 2 (EZH2). Cell lines with a high and low HCP5 expression were screened, and a pcDNA-3.1-HCP5 overexpression vector, small interfering RNA against HCP5, miR-138-5p mimics and miR-138-5p inhibitors were transfected into the CSCC cells. Cell viability, invasion, migration, apoptotic rate and autophagy were evaluated. The effects of HCP5 on autophagy and apoptosis of CSCC cells were verified in vivo using Ki67 and TUNEL staining. EZH2 was demonstrated to be upregulated in CSCC cells. miR-138-5p target sequences were identified in HCP5 and EZH2. HCP5 was revealed to function as a putative ceRNA of miR-138-5p to positively regulate EZH2, and EZH2 was shown to regulate autophagy and apoptosis of CSCC cells through the STAT3/VEGFR2 pathway. HCP5 overexpression decreased miR-138-5p levels, increased EZH2 levels and promoted cell malignant behaviors and autophagy but decreased the apoptosis rate. These trends were opposite when HCP5 was silenced. In conclusion, HCP5 may competitively bind to miR-138-5p to regulate EZH2 in CSCC cells, promoting autophagy and reducing apoptosis through the STAT3/VEGFR2 pathway. This study may provide a new perspective for understanding the molecular mechanism and treatment of CSCC.

Downregulation of long noncoding RNA HCP5/miR-216a-5p/ZEB1 axis inhibits the malignant biological function of laryngeal squamous cell carcinoma cells

“…In addition, HCP overexpression enhanced chemoresistance in gastric cancer and esophageal carcinoma (19,20). Besides this, HCP5 was prominently upregulated and acted as an oncogene in pancreatic cancer, bladder cancer, gastric cancer, and cutaneous squamous cell carcinoma (21)(22)(23)(24). Consistent with previous reports of other cancers, HCP5 expression was also upregulated in LSCC cells, and HCP5 was an oncogene.…”

“…Besides this, lncRNA is elucidated to enhance the expression of targeted genes by sponging with miRNAs (33). HCP5 promotes cancer development by sponging miR-140-5p, miR −138−5p, miR-29b-3p, and miR-143-3p (21)(22)(23)(24). In addition, HCP5 can sponge miR-216a-5p in cervical cancer (34).…”

Long non-coding RNA ZFY-AS1 represses periodontitis tissue inflammation and oxidative damage via modulating microRNA-129-5p/DEAD-Box helicase 3 X-linked axis

“…In order to intuitively observe the apoptosis of periodontal tissues, apoptotic cells were detected by TUNEL staining as mentioned above [ 20 ]. Processing of the sections and staining with TUNEL reactive mixture were in line with manufacturer’s instructions (Wanleibio Co., Ltd.).…”

Autophagy and Skin Diseases

“…As a result, increasing WWOX levels in cancer cells may be a potential method of suppressing autophagy (Tsai et al, 2013). Additionally, the most recent finding has demonstrated that inhibiting autophagy via silencing human histocompatibility leukocyte antigen complex P5 (HCP5) decreased the enhancer of zeste homolog 2 (EZ2H) expression and inhibited the STAT3/VEGFR2 pathway via competitive binding to miR-138-5p, which resulted in apoptosis in SCC cells (Zou et al, 2021).…”