A Novel Long Non-Coding RNA, SOX21-AS1, Indicates a Poor Prognosis and Promotes Lung Adenocarcinoma Proliferation

Abstract

Background:In recent years, long non-coding RNAs (lncRNAs) have been shown to be a novel class of regulators of cancer biological processes. Although lncRNAs are dysregulated in numerous cancer types, limited data are available on the expression profiles and potential functions of lncRNAs in lung adenocarcinoma (LUAD). This study evaluated the expression and biological roles of lncRNA SOX21 antisense RNA 1 (SOX21-AS1) in LUAD. Methods: Quantitative reverse transcription PCR (qRT-PCR) was performed to detect the expression levels of SOX21-AS1 in 68 pairs of LUAD tissues and corresponding non-tumor tissues. The effect of SOX21-AS1 on proliferation was evaluated by MTT, colony formation, EdU assays, flow-cytometric analysis and in vivo tumor formation assays. Real-time PCR, western-blot and immunohistochemistry were used to evaluate the mRNA and protein expression of p57. Results: Higher expression levels of SOX21-AS1 positively correlated with tumor size and advanced tumor-node-metastasis (TNM) stage. Multivariate analyses indicated that SOX21-AS1 expression could serve as an independent prognostic factor for overall survival of LUAD. Furthermore, knockdown of SOX21-AS1 significantly inhibited LUAD cell proliferation both in vitro and in vivo and induced cell cycle phase arrest and cell apoptosis. Importantly, through qRT-PCR and western blot analysis, we found that inhibition of SOX21-AS1 remarkably induced p57 expression. Conclusions: Collectively, our study demonstrates that SOX21-AS1 is involved in the development and progression of LUAD and that SOX21-AS1 may be a potential diagnostic factor as well as a target for new therapies for patients with LUAD.X. Lu, C. Huang and X. He contributed equally to this work.

Long non-coding RNA SOX21-AS1 modulates breast cancer stem cells properties and carcinogenesis via targeting SOX2

“…In oral squamous cell carcinoma, the aberrant promoter hypermethylation of SOX21-AS1 decreased the SOX21-AS1 expression and was significantly correlated with an advanced stage [14]. In lung adenocarcinoma, the higher expression levels of SOX21-AS1 positively correlated with tumor size and advanced TNM stage, and SOX21-AS1 knockdown significantly inhibited lung adenocarcinoma cells proliferation and metastasis [15]. Thus, the oncogenic role of SOX21-AS1 has verified once more in breast cancer.…”

“…LncRNA SOX21-AS1 has been reported to be correlated with tumorigenesis [14]. In lung adenocarcinoma, the unusual overexpression levels of SOX21-AS1 is positively correlated with tumor size and advanced tumor-nodemetastasis (TNM) stage, and the inhibition of SOX21-AS1 remarkably induced p57 expression [15].…”

Predicting functional long non-coding RNAs validated by low throughput experiments

“…SNHG20 regulated cell growth through modulation of a series of cell cycle-associated genes. Similarly, Lu et al [47] found that a higher expression level of a lncRNA, SOX21-AS1, positively correlated with the tumour size and the advanced stage of tumor-node-metastasis (TNM), and the inhibition of SOX21-AS1 induced p57 expression. SNHG20 and SOX21-AS1 are classified as EVlncRNAs by EVlncRNA-pred.…”

LncRNA ZFPM2‐AS1 promotes lung adenocarcinoma progression by interacting with UPF1 to destabilize ZFPM2

“…Long noncoding RNAs (lncRNAs), defined as non‐protein‐coding transcripts with more than 200 nucleotides, have been demonstrated to be novel participants in cancer‐related biological processes (Liu et al , ; Prensner et al , ; Wang et al , ; Wang et al , ). Also, increasing studies have revealed the regulatory functions of lncRNAs in LUAD (Lu et al , ; Qiu et al , ; Zhang et al , ). LncRNA zinc finger protein multitype 2 (ZFPM2) antisense RNA 1 (ZFPM2‐AS1) has been identified to exert promoting effect on gastric cancer progression through stabilizing MIF and inhibiting p53 pathway (Kong et al , ), but whether it has an impact in LUAD remains unknown.…”