Epithelial ovarian cancer (EOC) is one of the most malignant gynecological tumors worldwide. Deregulation of long non-coding RNAs (lncRNAs) has been implicated in various oncogenic processes in multiple cancers. In this study, we aim to identify and characterize clinically relevant lncRNA deregulation in EOC. LncRNAs, mRNAs and miRNAs were profiled using expression microarrays and validated using reverse transcription quantitative PCR in EOC cells and tissues. siRNAs targeting either HOXD-AS1 or PIK3R3 together with miR-186-5p inhibitors were used to modulate endogenous target expression in EOC cell lines in vitro. In vitro wound healing assay, trans-well assay, Western-blot assay,and Dual-luciferase reporter assay were used to explore the biological roles and molecular function underlying HOXD-AS1 in the EOC cells. Progression-free survival (PFS) and overall survival (OS) were statistically analyzed by Kaplan-Meier method test. HOXD-AS1 was found to be significantly over-expressed in EOC tumors. High HOXD-AS1 expression significantly correlated with poorer PFS and OS of EOC patients. Multivariate Cox proportional hazards modeling indicated that HOXD-AS1 was an independent risk predictor of EOC patients (HR = 1.92, p = 0.004). SiRNA inhibition of HOXD-AS1 reduced cell migration, invasion, and epithelial-mesenchymal transition (EMT) in EOC cells in vitro by preventing HOXD-AS1 directly binding to miR-186-5p, and resulting in down-regulating of PIK3R3. The novel HOXD-AS1/miR-186-5p/PIK3R3 pathway was clinically relevant as we observed a significantly inverse correlation between HOXD-AS1/miR-186-5p and between miR-186-5p/PIK3R3 in an independent cohort of 200 EOC tissues. HOXD-AS1/miR-186-5p/PIK3R3 is a novel pathway to promote cell migration, invasion, and EMT in EOC.

Colorectal cancer (CRC) is one of the most prevalent malignancies affecting the gastrointestinal tract and is ranked third among cancers with the highest incidence and second-highest mortality rate worldwide. CRC exhibits a slow progression providing a wide treatment window. The currently employed CRC screening methods have shown great potential to prevent CRC and reduce CRC-related morbidity and mortality. The diagnosis of CRC is achieved by colonoscopy and tissue biopsy, with studies showing that liquid biopsy is more effective in detecting and diagnosing early CRC patients. Increasing number of studies have shown that the tumor components shed into circulating blood can be detected in liquid form, and can be applied in the clinical management of CRC. Analysis of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), or tumor-associated platelets (TEPs) in the blood can be used for early screening and diagnosis of CRC, aid tumor staging, treatment response monitoring, and prediction of CRC recurrence and metastasis in a minimally invasive manner. This chapter provides an updated review of CTCs, ctDNA, and TEPs as novel biomarkers for CRC, highlighting their strengths and limitations.

Lack of animal model of radiation induced muscle fibrosis, this study aimed to establish such a model by using 90 Gy single dose irradiation to mimic clinical relevance and also to explore the potential post-irradiation regenerative mechanism. SD rats were randomly divided into dose investigation groups and time gradient groups. Group1–6 were irradiated with a single dose of 65Gy, 70Gy, 75Gy, 80Gy, 85Gy and 90Gy respectively, and the degree of rectus femoris fibrosis in the irradiated area was detected at 4 weeks after irradiation. Group 7–9 were irradiated with a single dose of 90Gy, and the results were detected 1, 2, 4, and 8 weeks after irradiation. Then the general condition of rats was recorded. Masson staining was used to detect muscle fibrosis. The ultrastructure of muscles was observed by electron microscope, and the expression changes of satellite cell proliferation and differentiation related genes were detected by quantitative real-time-PCR. A single dose of 90Gy irradiation could cause muscle fibrosis in rats. As time goes on, the severity of muscle fibrosis and the expression of TGF- β1 increased. Significant swelling of mitochondria, myofilament disarrangement and dissolution, obvious endothelial cell swelling, increased vascular permeability, decrease of blood cell, deposition of fibrosis tissue around the vessel could be found compared with the control group. At around the 4th week, the expressions of Pax7, Myf5, MyoD, MyoG, Mrf4 increased. Irradiation of 90Gy can successfully establish the rat model of radiation-induced muscle fibrosis. This model demonstrated that regenerative process was initiated by the irradiation only at an early stage, which can serve a suitable model for investigating regenerative therapy for post-radiation muscle fibrosis.

Mounting evidence suggests that immune cell infiltration within the tumor microenvironment (TME) is a crucial regulator of carcinogenesis and therapeutic efficacy in ovarian cancer (OC). In this study, 593 OC patients from TCGA were divided into high and low score groups based on their immune/stromal scores resulting from analysis utilizing the ESTIMATE algorithm. Differential expression analysis revealed 294 intersecting genes that influencing both the immune and stromal scores. Further Cox regression analysis identified 34 differentially expressed genes (DEGs) as prognostic-related genes. Finally, the nine-gene signature was derived from the prognostic-related genes using a Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression. This nine-gene signature could effectively distinguish the high-risk patients in the training (TCGA database) and validation (GSE17260) cohorts (all p < 0.01). A time-dependent receiver operating characteristic (ROC) analysis showed that the nine-gene signature had a reasonable predictive accuracy (AUC = 0.707, AUC =0.696) in both cohorts. In addition, this nine-gene signature is associated with immune infiltration in TME by Gene Set Variation Analysis (GSVA), and can be used to predict the survival of patients with OC.

Long non-coding RNAs (lncRNAs) play a crucial role in the occurrence and progression of various cancers. HOXD-AS1, an antisense RNA 1 of the lncRNA HOXD cluster, (also known as HAGLR, MIR7704HG, Mdgt, and STEEL), is located at human chromosome 2q31.1. Recent studies have demonstrated that the abnormal expression of HOXD-AS1 is significantly correlated with the clinicopathological features of patients with various tumors. The expression of HOXD-AS1 is abnormal in various tumors, affecting tumor cell proliferation, apoptosis, metastasis, invasion, metabolism, and drug resistance. HOXD-AS1 is important for cancer diagnosis and prognosis evaluation. Detecting its expression level helps judge cancer progression and predict patient survival. It is a therapeutic target and biomarker for early diagnosis and prognosis, with good clinical application prospects. This article reviews the role, molecular mechanisms, and potential clinical value of HOXD-AS1 in malignant tumor development.