Long non-coding RNA C5orf66-AS1 prevents oral squamous cell carcinoma through inhibiting cell growth and metastasis

Abstract

Oral squamous cell carcinoma (OSCC) is a major cancer type in the head and neck region. Recent studies have reported a marked rise in the incidence of OSCC. The present study was performed to better understand the roles that long non-coding RNAs (lncRNAs) serve in OSCC carcinogenesis. The levels of the lncRNA C5orf66 antisense RNA 1 (C5orf66-AS1) and of cytochrome c1 (CYC1) in OSCC tissues and cells were measured through reverse transcription-quantitative polymerase chain reaction. In addition, the levels of associated proteins were analyzed by western blotting, while MTT assay was used to detect the cell proliferation ability. Wound healing and transwell assays were also used to detect the migration and invasion abilities of OSCC cells in the experimental groups, while flow cytometry was applied to analyze cell apoptosis. The findings revealed that the expression of lncRNA C5orf66-AS1 in OSCC tissues and cells was significantly decreased. Overexpression of lncRNA C5orf66-AS1 significantly inhibited the proliferation, invasion and migration ability of OSCC cells, and promoted cell apop-tosis, while lncRNA C5orf66-AS1 downregulation presented the opposite effects. In addition, it was observed that CYC1 was upregulated in OSCC tissues and cells, and was negatively regulated by lncRNA C5orf66-AS1. Notably, CYC1 silencing markedly eliminated the effects of lncRNA C5orf66-AS1 downregulation on OSCC cells. Taken together, these findings indicated that lncRNA C5orf66-AS1 may prevent OSCC progression by inhibiting OSCC cell growth and metastasis via the regulation of CYC1 expression.

Epigenetic Modifications in Head and Neck Cancer

“…Shen et al (2018) reported that higher expression of AC026166.2-001 suppressed cell proliferation and migration in LSCC cells, inhibited cells cycle, and supported cell apoptosis in laryngeal cancer. Also other lncRNAs are upregulated in HNSCC and may display oncogenic properties, such as ZFAS1 (Kolenda et al 2019), PVT1 (Yu et al 2018), CASC9 (Sassenberg et al 2019), TUG1 (Zhang et al 2018b), MIAT (Zhong et al 2019), SNHG20 (Wu et al 2019), or RGMB-AS (Xu and Xi 2019), or downregulated and may act as tumor suppressor genes, such as STR5-AS (Wang et al 2019a), C5orf66-AS1 (Lu et al 2018), AC012456.4 (Hu et al 2018b), LINC01133 (Kong et al 2018), ZNF667, and ZNF667-AS1 (Meng et al 2019).…”

<p>Evaluation of C5orf66-AS1 as a Potential Biomarker for Predicting Early Gastric Cancer and Its Role in Gastric Carcinogenesis</p>

“…Guo et al 21 reported that C5orf66-AS1 was upregulated in esophageal cancer cells, the expression of proliferation-related indicators Ki-67 and PCNA was downregulated, the expression of EMT-related proteins N-cadherin and Vimentin was downregulated, and the E-cadherin involved in the invasion and metastasis pathway was upregulated, suggesting that C5orf66-AS1 inhibited the proliferation and metastasis of esophageal cancer cells. 21 Lu et al 19 reported that CYC1 was negatively regulated by C5orf66-AS1 in oral squamous cell carcinoma, and the biological behavior (invasion, metastasis, proliferation, and apoptosis) could be reversed by knocking down CYC1. Rui et al 23 reported that C5orf66-AS1 could promote the proliferation, invasion, and metastasis of cervical cancer cells and inhibit the apoptosis of cervical cancer cells by competing with RING1 in combination with miR-637.…”

“…15,16 These characteristics provide a theoretical basis for considering lncRNAs as biomarkers for cancer. It has been reported that lncRNA can participate in series of pathological processes in tumorigenesis, for instance, inflammatory response, 17 autophagy, 18 pyroptosis, 19 metabolic reprogramming, 18 as well as crosstalk between immune cells and tumor cells 20 and immunotherapy resistance. 21 The extensive functions of lncRNAs suggest extremely valuable for research.…”

“…C5orf66-AS1 (also named CTC-276P9.1 or Epist) is an antisense lncRNA present at the first intron region of C5ORF66, which is located on chromosome 5 (chr5: 135, 038, 831-135, 040, 047; size: 1, 217), containing two exons. A few studies reported that downregulation of C5orf66-AS1 was associated with pituitary null cell adenomas, 17 oral squamous cell carcinoma, 18,19 head and neck squamous cell carcinomas, 20 esophageal squamous cell carcinoma, 21 and bladder cancer; 22 however, it was upregulated in cervical cancer. 23 Aberrant hypermethylation-mediated downregulation of C5orf66-AS1 might serve as a potential prognostic biomarker for cardia adenocarcinoma.…”

Research Progress on lncRNA Functions and Mechanisms in Pituitary Adenomas

“…The lncRNA c5orf66-as1 (also known as Epist and ctc-276p9.1) is located in human chromosome 5q31.1. Studies have shown that the expression of c5orf66-as1 is downregulated in esophageal squamous cell carcinoma, oral squamous cell carcinoma, and cardiac carcinoma [80][81][82][83], meaning that this lncRNA may act as a tumor suppressor, and that it constitutes a potential marker for patient prognosis and survival. Interestingly, Rui et al [84] reported that in cervical cancer tissues and cells, c5orf66-as1 is significantly upregulated.…”