MiR‐15b/HOTAIR/p53 form a regulatory loop that affects the growth of glioma cells

Abstract

Among the malignant tumors of the human central nervous system, gliomas have the highest incidence and recurrence rate. Therefore, exploration of the molecular mechanism that underlies the development and progression of gliomas is of great clinical significance. Many studies have demonstrated that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play important roles in the development and progression of tumors. In the present study, both an RNAhybrid analysis and a dual-luciferase reporter gene assay confirmed that microRNA-15b (miR-15b) binding sites were present in the sequence of HOX transcript antisense RNA (HOTAIR). The present study further demonstrated that miR-15b, HOTAIR, and p53 formed a mutually regulated loop. MiR-15b upregulated the expression of p53 but inhibited the expression of HOTAIR. In addition, miR-15b was able to regulate the expression of HOTAIR through p53. P53 promoted miR-15b expression but inhibited HOTAIR expression. Furthermore, the examination of cell proliferation, apoptosis, and invasion revealed that both miR-15b and p53 inhibited the proliferation and invasion, but promoted the apoptosis, of glioma cells. In contrast, HOTAIR exerted effects that were the opposite of those exerted by miR-15b and p53 on glioma cells. The upregulation of HOTAIR suppressed the inhibitory effects of miR-15b and p53 on cell proliferation and invasion as well as the promoting effect of miR-15b and p53 on apoptosis. Therefore, it can be concluded that miR-15b, HOTAIR, and p53 constitute a regulatory loop that is capable of regulating the growth of glioma cells. This finding provides a new target for the treatment of gliomas.

Deregulated lncRNA expression profile in the mouse lung adenocarcinomas with KRAS‐G12D mutation and P53 knockout

“…Furthermore, some lncRNAs have been demonstrated to be aberrantly expressed in lung cancer tissues and be associated with cancer progression. For example, HOTAIR is up‐regulated in lung cancer specimens and displayed potential tumour‐promoting roles ; MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells, as a competing endogenous RNA (ceRNA) to regulate autophagy‐related 7 (ATG7) gene expression by sponging miR142‐3p …”

“…24 Furthermore, some lncRNAs have been demonstrated to be aberrantly expressed in lung cancer tissues and be associated with cancer progression. For example, HOTAIR is up-regulated in lung cancer specimens and displayed potential tumour-promoting roles [25][26][27] ;…”

The Roles of lncRNA in Cutaneous Squamous Cell Carcinoma

“…These two genes not only are closely related to the human embryonic development but also played a key regulatory role in the adult organ and tissue formation (66). HOTAIR is widely involved in the regulation of the malignant process such as proliferation, apoptosis, angiogenesis, invasion, and metastasis (67). HOTAIR monitored epigenetic modification by the histone H3K27me3 (68) and regulated WIF-1 and PTEN, thereby effecting the Wnt and Akt signaling pathways (69,70).…”

Oligonucleotide Therapeutics as a New Class of Drugs for Malignant Brain Tumors: Targeting mRNAs, Regulatory RNAs, Mutations, Combinations, and Beyond

“…The most studied among them is HOTAIR, a HOX transcript antisense RNA that promotes glioma cell cycle, growth, and angiogenesis [ 331 , 332 ]. The mechanism of its function in glioma is not fully investigated and may include EZH2-dependent epigenetic regulation [ 333 ], as well as regulation of β-catenin signaling [ 334 ] and perturbed miRNA binding [ 335 – 337 ]. Another lncRNA H19 is processed from the H19-IGF2 loci, can be induced by c-myc and HIF1α, and is upregulated in glioma and other malignancies [ 338 , 339 ].…”