Upregulated circular RNA circ_0070934 facilitates cutaneous squamous cell carcinoma cell growth and invasion by sponging miR-1238 and miR-1247-5p.

Accumulating studies have appreciated circular RNAs (circRNAs) as novel prognostic biomarkers and therapeutic targets in malignant carcinomas. Here, we aim to investigate the expression of a novel circRNA, circ_0070934. The biological roles and mechanisms of circ_0070934 in cutaneous squamous cell carcinoma (CSCC) were explored. The expression of circ_0070934 in CSCC tissues and cell lines was evaluated by qRT-PCR. Loss-of-function and gain-of-function assays were performed to detect cell proliferation, apoptosis, migration and invasion in vitro. Moreover, the underlying molecular mechanism of circ_0070934 was predicted by online database and luciferase reporter assay. Abnormally overexpression of circ_0070934 was detected in CSCC samples and cell lines. Inhibition of cell proliferation, invasion, migration, and increased apoptosis were observed upon circ_0070934 knockdown. The opposite effect was observed in the circ_0070934 overexpression cells. Circ_0070934 expression was negatively correlated with miR-1238 and miR-1247-5p expression in CSCC and luciferase reporter experiment verified the binding ability between circ_0070934 and miR-1238/miR-1247-5p. Rescue experiments further identified that the oncogenic role of circ_0070934 is attributed to its suppression of miR-1238 and miR-1247-5p. Taken together, our results implicate that circ_0070934 is correlated with tumor aggressiveness by serving as an oncogenic circRNA in CSCC.

An X ，Liu X ，Ma G ，Li C ... -  《-》

Circular RNA circ-LARP1B contributes to cutaneous squamous cell carcinoma progression by targeting microRNA-515-5p/TPX2 microtubule nucleation factor axis.

Wang L ，Hou S ，Li J ，Tian T ，Hu R ，Yu N ... -  《-》

CircRNA circ_0067772 aggravates the malignant progression of cutaneous squamous cell carcinoma by regulating miR-1238-3p/FOXG1 axis.

Li X ，Kong Y ，Li H ，Xu M ，Jiang M ，Sun W ，Xu S ... -  《-》

Hsa_circ_0008234 facilitates proliferation of cutaneous squamous cell carcinoma through targeting miR-127-5p to regulate ADCY7.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignant tumor with 25-50% of 5-year survival. There exist urgent needs for the identification of novel biomarkers for the diagnostic and therapeutic strategies of cSCC. The differentially expressed circRNAs in cSCC tissues and non-lesional skin tissues were obtained through analyzing the circular RNAs (circRNAs) microarray dataset GSE74758. The expression pattern of the indicated circRNAs in cSCC tissues was confirmed by qRT-PCR. FISH analysis was used to detect the location of hsa_circ_0008234 in cells. RIP experiment was used to detect the interaction between hsa_circ_0008234 and miR-127-5p. CCK-8 analysis and colony formation assay were used to detect the proliferation of cSCC cells. qRT-PCR and western blot were adopted to detect the expression of ACDY7. Three differential expressed circRNAs were obtained from the microarray data (GSE74758), and hsa_circ_0008234 was confirmed to be highly expressed in cSCC tissues by qRT-PCR. Hsa_circ_0008234 was mainly located in cytoplasm and stable in cSCC cells. RIP experiment revealed that hsa_circ_0008234 directly interacts with miR-127-5p in cSCC cells. Hsa_circ_0008234 increased the cell viability and colony formation of cSCC cells through acting as the sponge of miR-127-5p. MiR-127-5p inhibited the expression of ADCY7 in cSCC cells through binding the 3'UTR of ADCY7. Hsa_circ_0008234 was positively associated with ADCY7 expression in cSCC tissues. Hsa_circ_0008234 facilitates the proliferation of cSCC through targeting miR-127-5p to regulate ADCY7 expression and has the potential to be a novel therapeutic target for cSCC.

Cai L ，Wang Y ，Wu J ，Wu G ... -  《-》

Circ_0001402 knockdown suppresses the chemoresistance and development of DDP-resistant cutaneous squamous cell carcinoma cells by functioning as a ceRNA for miR-625-5p.

Cutaneous squamous cell carcinoma (CSCC) is the most common metastatic skin cancer. Circular RNAs (circRNAs) are differentially expressed in CSCC and can sequester and sponge microRNAs. GSE74758 shows that hsa_circ_0001402 (circ_0001402) is the most overexpressed circRNA in CSCC. Expression of circ_0001402, microRNA(miR)-625-5p and karyopherin subunit alpha 4 (KPNA4) was detected by quantitative real-time polymerase chain reaction and/or Western blot. Colon formation, flow cytometry, Transwell assays and xenograft tumour model confirmed the development of CSCC cells. The competing endogenous RNA (ceRNA) interaction was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Circ_0001402 was significantly upregulated in CSCC tissues and cells, and higher expression of circ_0001402 was found in DDP-resistant samples. Functionally, circ_0001402 knockdown induced apoptosis and inhibited half maximal inhibitory concentration of DDP, colony formation, migration and invasion of DDP-resistant CSCC cells, accompanied with the depressed multi-drug resistance-1 (MDR1) and MDR-related protein-1, while miR-625-5p inhibitor could counteract these effects. Mechanically, circ_0001402 mediated the expression regulation of KPNA4 via functioning as a ceRNA for miR-625-5p. KPNA4 re-expression could abate the functions of miR-625-5p. Furthermore, circ_0001402 knockdown could hinder tumour growth of DDP-resistant CSCC. Circ_0001402 knockdown can suppress the development and chemoresistance of DDP-resistant CSCC cells at least partly through targeting miR-625-5p/KPNA4 axis.

Li M ，Luo M ，Liu P ，Wang R ，Jing H ... -  《-》