Antisense oncology

SRY-box transcription factor 21 antisense divergent transcript 1 (SOX21-AS1) is a multifaceted long non-coding RNA (lncRNA) that plays diverse roles in both neoplastic conditions and Alzheimer's disease. Its aberrant expression intricately regulates a wide spectrum of cellular processes, spanning from epithelial-mesenchymal transition (EMT), apoptosis, migration, metastasis, and stemness to drug resistance. SOX21-AS1 achieves these effects through its involvement in the competitive endogenous RNA (ceRNA) network, modulation of downstream genes, and regulation of critical pathways, including PI3K/AKT, Hippo, Wnt/β-catenin, and ERK signaling...

OBJECTIVE: We previously elucidated that long non-coding RNA Promoter of CDKN1A Antisense DNA damage Activated RNA (PANDAR) as a p53-dependent oncogene to promote cisplatin resistance in ovarian cancer (OC). Intriguingly, high level of p53-independent PANDAR was found in cisplatin-resistant patients with p53 mutation. Here, our study probed the new roles and the underlying mechanisms of PANDAR in p53-mutant OC cisplatin-resistance. METHODS: A2780 and A2780-DDP cells were served as OC cisplatin-sensitive and cisplatin-resistant cells...

Genomic imprinting, an epigenetic mechanism that regulates gene expression from parental chromosomes, holds substantial relevance in multiple cancers, including hematopoietic malignancies. In the present study, the expression of a panel of 16 human imprinted genes in bone marrow samples from 64 patients newly diagnosed with cytogenetically normal-acute myeloid leukemia (CN-AML) were examined alongside peripheral blood samples from 85 healthy subjects. The validated findings of the present study revealed significant upregulation of seven genes [COPI coat complex subunit gamma 2 ( COPG2 ), H19 imprinted maternally expressed transcript ( H19 ), insulin like growth factor 2 ( IGF2 ), PEG3 antisense RNA 1 ( PEG3-AS1 ), DNA primase subunit 2 ( PRIM2 ), solute carrier family 22 member 3 SLC22A3 and Zinc finger protein 215 ( ZNF215 )] in patients with CN-AML (P<0...

BACKGROUND/AIM: The interaction of integrin αvβ8 with type I collagen was shown to promote oral squamous cell carcinoma (SCC) cell proliferation via the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. However, the role of integrin αvβ8 in SCC progression remains poorly understood. In this study, the role of integrin αvβ8 in oral SCC progression was therefore investigated. MATERIALS AND METHODS: Integrin αv and β8 protein expression in oral SCC cells was examined by western blotting...

HOXC cluster antisense RNA 3 (HOXC-AS3) is a novel long noncoding RNA (lncRNA) that exhibits aberrant expression patterns in various cancer types. Its expression is closely related to clinicopathological features, demonstrating significant clinical relevance across multiple tumors. And HOXC-AS3 plays multifaceted roles in tumor progression, impacting cell proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition (EMT), autophagy, senescence, tumor growth, and metastasis. In this review, we summarized and comprehensively analyzed the expression and clinical significance of HOXC-AS3 as a diagnostic and prognostic biomarker for malignancies...

INTRODUCTION: Proteinkinase B (Akt), an essential protein in the PI3K/Akt/mTOR signalingpathway, plays a crucial role in tumor progression. Over the past twoyears, different types of Akt modulators have continued to emerge inthe patent literature. AREASCOVERED: Thisreview focuses on the patent literature covering small moleculeinhibitors, peptides, PROTACs, and antisense nucleic acids targetingAkt from 2020 to present. Also, we discuss the outcomes of severalclinical trials, combination strategies for different mechanisms, andthe application of Akt regulators in other non-oncology indications...

Colorectal cancer (CRC) is a complex malignancy responsible for the second-highest cancer deaths worldwide. TGF-β maintains normal cellular homeostasis by inhibiting the cell cycle and inducing apoptosis, but its elevated level is correlated with colorectal cancer progression, as TGF-β is a master regulator of the epithelial-to-mesenchymal transition, a critical step of metastasis. Tumors, including CRC, use elevated TGF-β levels to avoid immune surveillance by modulating immune cell differentiation, proliferation, and effector function...

Precision medicine in oncology has made significant progress in recent years by approving drugs that target specific genetic mutations. However, many cancer driver genes remain challenging to pharmacologically target ("undruggable"). To tackle this issue, RNA-based methods like antisense oligonucleotides (ASOs) that induce targeted exon skipping (ES) could provide a promising alternative. In this work, a comprehensive computational procedure is presented, focused on the development of ES-based cancer treatments...

Alternative polyadenylation (APA), a posttranscriptional mechanism of gene expression via determination of 3'UTR length, has an emerging role in carcinogenesis. Although abundant APA reprogramming is found in kidney renal clear cell carcinoma (KIRC), which is one of the major malignancies, whether APA functions in KIRC remains unknown. Herein, we found that chromatin modifier MORC2 gained oncogenic potential in KIRC among the genes with APA reprogramming, and moreover, its oncogenic potential was enhanced by 3'UTR shortening through stabilization of MORC2 mRNA...

Dysregulation of long non‑coding RNAs (lncRNAs) is involved in the development of colorectal cancer (CRC). In the present study, the identification of muscle blind like splicing regulator 1 antisense RNA 1 (MBNL1‑AS1) lncRNA was reported. Firstly, Cell Counting Kit‑8, EdU and colony formation assays were uesed to explore the role of MBNL1‑AS1 in regulating the proliferation of CRC cells. According to TCGA database, it was found that MBNL1‑AS1 was correlated with microRNA (miR)‑29c‑3p and blood vessel epicardial substance (BVES) expression in CRC cells...

Neoadjuvant chemo-immunotherapy improves pathological complete response rate and event-free survival in patients with resectable non-small-cell lung cancer (NSCLC), versus chemotherapy alone. NeoCOAST was the first randomized, multi-drug, platform trial to examine novel neoadjuvant immuno-oncology combinations for patients with resectable NSCLC, using major pathological response (MPR) as the primary endpoint. Eighty-three patients received a single cycle of treatment: 26 received durvalumab (anti-PD-L1) monotherapy, 21 received durvalumab plus oleclumab (anti-CD73), 20 received durvalumab plus monalizumab (anti-NKG2A), and 16 received durvalumab plus danvatirsen (anti-STAT3 antisense oligonucleotide)...

BACKGROUND: Most of the endometrial cancer (EC) patients are diagnosis in early stage with a good prognosis while the patients with locally advanced recurrent or metastatic result in a poor prognosis. Adjuvant therapy could benefit the prognosis of patients with high-risk factors. Unfortunately, the molecular classification of great prognostic value has not yet reached an agreement and need to be further refined. The present study aims to identify new targets that have prognostic value in EC based on the method of EC patient-derived organ-like organs (PDOs), and further investigate their efficacy and mechanism...

PURPOSE: There is compelling evidence that long-stranded non-coding RNAs (lncRNAs) play an important role in the progression of hepatocellular carcinoma (HCC). The aim of this study was to investigate the role of lncRNA XXYLT1 antisense-2 (XXYLT1-AS2) in HCC progression. METHODS: Real-time PCR was used to assess the levels of XXYLT1-AS2 in plasma from HCC and normal patients. Cell proliferation, apoptosis, migration, and invasion were monitored, and tumor xenografts were established to investigate the biological functions of XXYLT1-AS2 by gain-of-function and loss-of-function studies in vitro and in vivo, the expression of autophagy biomarkers and transcriptional factor EB (TFEB) was examined by immunoprecipitation, ubiquitination assays, and western blotting...

BACKGROUND: Endometrial carcinoma (EC) is one of the world's typical female reproductive tract malignancies, mostly occurring in postmenopausal women. Many reports have confirmed that long non-coding RNA SOX21 antisense RNA1 (lncRNA SOX21-AS1) is associated with the progressions of various cancer. However, the mechanism of SOX21-AS1 in EC remains unclear. Our study is intended to probe the mechanisms of SOX21-AS1 on EC progression. METHODS: The CCK-8 assay and colony formation detected cell proliferation...

Accumulating evidence has indicated that long non-coding RNAs (lncRNAs) play critical roles in the development and progression of cancers, including esophageal squamous cell carcinoma (ESCC). However, the mechanisms of lncRNAs in ESCC are still incompletely understood and therapeutic attempts for in vivo targeting cancer-associated lncRNA remain a challenge. By RNA-sequencing analysis, we identified that LLNLR-299G3.1 was a novel ESCC-associated lncRNA. LLNLR-299G3.1 was up-regulated in ESCC tissues and cells and promoted ESCC cell proliferation and invasion...

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Owing to a lack of effective treatments, patients with metastatic disease have a median survival time of 6-12 months. We recently demonstrated that the Survival Associated Mitochondrial Melanoma Specific Oncogenic Non-coding RNA (SAMMSON) is essential for UM cell survival and that antisense oligonucleotide (ASO)-mediated silencing of SAMMSON impaired cell viability and tumor growth in vitro and in vivo . By screening a library of 2911 clinical stage compounds, we identified the mammalian target of rapamycin (mTOR) inhibitor GDC-0349 to synergize with SAMMSON inhibition in UM...

The MAF bZIP transcription factor G-antisense RNA 1 (MAFG-AS1) is located on chromosome 17. MAFG-AS1 was upregulated in 15 human cancers. MAFG-AS1 not only suppresses 16 miRNAs but also directly impacts 22 protein-coding genes' expression. Notably, abnormal MAFG-AS1 expression is connected to clinicopathological characteristics and a worse prognosis in a variety of cancers. Moreover, MAFG-AS1 takes its part in the tumorigenesis and progression of various human malignancies by suppressing apoptosis and promoting proliferation, migration, invasion, aerobic glycolysis, ferroptosis, angiogenesis, EMT, and metastasis...

BACKGROUND: Although immune checkpoint inhibitors have been a breakthrough in clinical oncology, these therapies fail to produce durable responses in a significant fraction of patients. This lack of long-term efficacy may be due to a poor pre-existing network linking innate and adaptive immunity. Here, we present an antisense oligonucleotide (ASO)-based strategy that dually targets toll-like receptor 9 (TLR9) and programmed cell death ligand 1 (PD-L1), aiming to overcome resistance to anti-PD-L1 monoclonal therapy...

PURPOSE: HOX transcribed antisense RNA (HOTAIR) is a long noncoding RNA (LncRNA) that promotes tumor progression. Exosomes are critically involved in cancer progression. The presence of HOTAIR in the circulating exosomes and the roles of exosomal HOTAIR in gastric cancer (GC) remains unknown. This study aimed to investigate the role of HOTAIR in exosomes in promoting the growth and metastasis of GC. METHODS: Serum exosomes from GC patients were captured by CD63 immunoliposome magnetic spheres (CD63-IMS), and the biological characteristics of the exosomes were identified...

Since prostate cancer (PCa) was described as androgen-dependent, the androgen receptor (AR) has become the mainstay of its systemic treatment: androgen deprivation therapy (ADT). Although, through recent years, more potent drugs have been incorporated, this chronic AR signaling inhibition inevitably led the tumor to an incurable phase of castration resistance. However, in the castration-resistant status, PCa cells remain highly dependent on the AR signaling axis, and proof of it is that many men with castration-resistant prostate cancer (CRPC) still respond to newer-generation AR signaling inhibitors (ARSis)...