Long non-coding RNA TP73-AS1 in cancers

Highlights

• TP73-AS1 is dysregulated in multiple cancers.

• TP73-AS1 is an important target for regulating the biological functions of tumour cells.

• TP73-AS1 is an important competitive endogenous RNA (ceRNA) in human cancers.

Abstract

More and more evidence indicates that long non-coding RNAs (lncRNAs), as a kind of non-coding endogenous single-stranded RNA, play an essential role as oncogenes or tumour suppressors in the occurrence and development of human cancers. The tumour protein P73 antisense RNA 1 (TP73-AS1) was initially found to be down-regulated in oligodendroglioma and may act as a non-protein-encoding RNA. Since its discovery, TP73-AS1 has been identified as a carcinogenic regulator of many malignancies. At the same time, the high expression of TP73-AS1 is related to the clinicopathological features of patients with cancer. It also regulates cell proliferation, anti-apoptosis, invasion and metastasis through a variety of potential mechanisms, suggesting that it may be a promising biomarker and therapeutic target for cancer. In this review, we summarize the biological functions, mechanisms, and potential clinical implications of TP73-AS1 dysregulation in tumourigenesis and progression.

Introduction

Worldwide, cancer is a major cause of high mortality and disability, causing great personal suffering and social or economic burden [1]. Although conventional surgical treatment, chemotherapy and radiotherapy can improve the quality of patients life, they often have limited therapeutic effects [2]. Therefore, the exploration of molecular markers and therapeutic targets is vital for the early diagnosis of cancer.

Long non-coding RNAs (lncRNAs) are transcripts that are more than 200 nucleotides in length and are mediated by RNA polymerase II without protein-encoding ability [3], [4]. They play a vital role in a variety of biological processes by regulating chromatin organization, transcriptional regulation and post-transcriptional regulation [5], [6]. Meanwhile, in human cancers, more and more evidence shows that the abnormal expression of lncRNAs is related to the occurrence, progression, metastasis and prognosis of various tumours, which may be used as biomarkers for cancer diagnosis and prognosis [7], [8], [9].

The tumour protein P73 antisense RNA 1 (TP73-AS1) is an lncRNA located at 1p36.32, and is also known as p53-dependent apoptosis modulator (PDAM) or KIAA0495. The tumour protein P73, a member of the p53 tumour suppressor family, regulates many biological processes, such as cell cycle arrest, apoptosis, neurogenesis, cancer and metabolism, and is the major oncogene responsible for human cancer development and chemotherapy resistance [10]. In 2010, it was first demonstrated that PDAM is down-regulated in oligodendrogliomas, and that chromosome 1p loss and epigenetic modification are the main mechanisms of down-regulation and may act as non-protein-encoding RNAs [11]. Since that revelation, research on TP73-AS1 in human cancer has gradually increased. In recent years, there has been increasing evidence that TP73-AS1 is abnormally expressed in human multisystem cancers (see Fig. 1), including hepatocellular carcinoma [12], glioma [13], bladder cancer [14], breast cancer [15], Osteosarcoma [16], cervical cancer [17]. In addition, TP73-AS1 is also involved in the regulation of cancer cell proliferation, apoptosis, migration and invasion processes. In this review, we summarize the role of TP73-AS1 expression dysregulation in the development and progression of multisystem cancer, related mechanisms (Fig. 2), and potential clinical implications (see Table 1, Table 2).