Long non-coding RNAs (LncRNAs) represent a novel class of noncoding RNAs that are longer than 200 nucleotides without protein-coding potential and function as novel master regulators in various human diseases, including cancer. Accumulating evidence shows that lncRNAs are dysregulated and implicated in various aspects of cellular homeostasis, such as proliferation, apoptosis, mobility, invasion, metastasis, chromatin remodeling, gene transcription, and post-transcriptional processing. However, the mechanisms by which lncRNAs regulate various biological functions in human diseases have yet to be determined. HOX antisense intergenic RNA (HOTAIR) is a recently discovered lncRNA and plays a critical role in various areas of cancer, such as proliferation, survival, migration, drug resistance, and genomic stability. In this review, we briefly introduce the concept, identification, and biological functions of HOTAIR. We then describe the involvement of HOTAIR that has been associated with tumorigenesis, growth, invasion, cancer stem cell differentiation, metastasis, and drug resistance in cancer. We also discuss emerging insights into the role of HOTAIR as potential biomarkers and therapeutic targets for novel treatment paradigms in cancer.

Circular RNA (circRNA) is an intriguing class of RNA with covalently closed-loop structure and is highly stable and conservative. As new members of the ncRNAs, the function, mechanism, potential diagnostic biomarker, and therapeutic target have raised increased attention. Most circRNAs are presented with characteristics of abundance, stability, conservatism, and often exhibiting tissue/developmental-stage-specific manner. Over 30,000 circRNAs have been identified with their unique structures to maintain stability more easily than linear RNAs. An increased numbers of circRNAs are dysregulated and involved in several biological processes of malignance, such as tumorigenesis, growth, invasion, metastasis, apoptosis, and vascularization. Emerging evidence suggests that circRNAs play important roles by acting as miRNA sponge or protein scaffolding, autophagy regulators, and interacting with RNA-binding protein (RBP), which may potentially serve as a novel promising biomarker for prevention, diagnosis and therapeutic target for treatment of human cancer with great significance either in scientific research or clinic arena. This review introduces concept, major features of circRNAs, and mainly describes the major biological functions and clinical relevance of circRNAs, as well as expressions and regulatory mechanisms in various types of human cancer, including pathogenesis, mode of action, potential target, signaling regulatory pathways, drug resistance, and therapeutic biomarkers. All of which provide evidence for the potential utilities of circRNAs in the diagnosis and treatment of cancer.

Berberine (BBR), a component from traditional Chinese medicine, has been shown to possess anti-tumor activity against a wide spectrum of cancer cells including human lung cancer, but the detailed mechanism underlining this has not been well elucidated.

HOTAIR is an important carcinogenic lncRNA and involves in tumorigenesis, and invasion. MiR‐34a‐5p functions as a tumour suppressor. However, the underlying mechanism of HOTAIR regulation especially in association with miR‐34a‐5p in non‐small‐cell lung cancer (NSCLC) has not been explored. Herein, we performed series of in vitro experiments, including viability, migration, invasion, apoptosis and in vivo xenograft model, and identified that HOTAIR was remarkably elevated in NSCLC cells. Enforced HOTAIR expression promoted migration and invasion, while depleted HOTAIR diminished the ability of migration and invasion of NSCLC cells. We also observed that miR‐34a‐5p was dramatically inhibited in NSCLC cells and the binding correlation between HOTAIR and miR‐34a‐5p was confirmed by dual‐luciferase reporter and RNA immunoprecipitation assays. We also showed that induction of miR‐34a‐5p and reduction of HOTAIR, and the interaction between miR‐34a‐5p and HOTAIR resulted in the suppression of epithelial‐mesenchymal transition (EMT) as illustrated by induction of key epithelial markers E‐cadherin expression, reduction of vimentin and EMT‐inducing transcription factor snail. Excessive expression of snail resisted miR‐34a‐5p‐inhibited cell growth. Snail binds to E‐cadherin promoter and regulates E‐cadherin expression. There was a synergy in combination of berberine and gefinitib in this process. Similar findings were also observed in a tumour xenograft model. Collectively, this is the first report demonstrating reciprocal interaction of miR‐34a‐5p‐ and HOTAIR‐mediated regulation of snail resulting in inhibition of EMT process by the combination of berberine and gefitinib suggesting that regulation of miR‐34a‐5p‐ and HOTAIR‐mediated inhibition of EMT may provide novel treatment paradigms for lung cancer.

PIWI-interacting RNAs (piRNAs) are a type of non-coding RNAs that interact with PIWI proteins, which are members of the argonaute family. Originally described in the germline, piRNAs are also expressed in human somatic cells in a tissue-specific manner. piRNAs are involved in spermatogenesis, germ stem-cell maintenance, silencing of transposon, epigenetic and genomic regulation and rearrangement. A large number of studies have demonstrated that expression of piRNAs is involved in many kinds of disease, including cancer. Abnormal expression of piRNAs is emerging as a critical player in cancer cell proliferation, apoptosis, invasion, and migration in vitro and in vivo. Functionally, piRNAs maintain genomic integrity by repressing the mobilization of transposable elements, and regulate the expression of downstream target genes via transcriptional or post-transcriptional mechanisms. Furthermore, altered expression of piRNAs in cancer is linked to clinical outcome, highlighting the important role that they may play as novel diagnostic and prognostic biomarkers, and as therapeutic targets for cancer therapy. In this review, we focus on the biogenesis and the functional roles of piRNAs in cancers, discuss emerging insights into the roles of piRNAs in the occurrence, progression, and treatment of cancers, reveal various mechanisms underlying piRNAs-mediated gene regulation, and highlight their potential clinical utilities as biomarkers as well as potential targets for cancer treatment.