HOXC13-AS promotes breast cancer cell growth through regulating miR-497-5p/PTEN axis.

Dysregulated long noncoding RNAs (lncRNAs) remains to be explored in tumorigenesis. LncRNA HOXC13 antisense RNA (HOXC13-AS) has been found as an oncogene in many cancers; however, the role of HOXC13-AS in breast cancer still elusive. In this study, the HOXC13-AS levels and its role in cell proliferation was first measured by real-time quantitative polymerase chain reaction, Cell Counting Kit-8 assay, and colony formation assay. It showed that HOXC13-AS was increased in breast cancer tissues compared with the adjacent normal tissues and upregulated HOXC13-AS promoted the growth of breast cancer cells. Then, we found that the miR-497-5p levels were downregulated in cancer tissues compared with the adjacent tissues and miR-497-5p suppressed breast cancer cell proliferation. Further study showed that HOXC13-AS could function as a "sponge" for miR-497-5p then suppress miR-497-5p expression. Moreover, we next identified that Phosphatase and Tensin homolog (PTEN) is the target of miR-497-5p. Overexpression of miR-497-5p by chemical mimics decreased the expression of PTEN, while downregulation of miR-497-5p by HOXC13-AS rescued the expression of PTEN. Finally, we showed that HOXC13-AS promoted the proliferation of breast cancer cells and tumor growth through miR-497-5p/PTEN axis in vitro and in vivo. Hence, we conclude that HOXC13-AS, which is significantly upregulated in breast cancers, promoted cell proliferation through the suppressed miR-497-5p and further upregulated PTEN.

Long noncoding RNA HOXC13-AS positively affects cell proliferation and invasion in nasopharyngeal carcinoma via modulating miR-383-3p/HMGA2 axis.

Long noncoding RNAs have been reported to be important regulators in numerous cancers. In this study, we found that HOXC13 antisense RNA (HOXC13-AS) was highly expressed in head and neck squamous carcinoma (HNSC) tissues in The Cancer Genome Atlas database. Nasopharyngeal carcinoma (NPC) belongs to HNSC. Therefore, we further investigated the potential role of HOXC13-AS in NPC. Quantitative reverse transcription polymerase chain reaction examination revealed that HOXC13-AS was markedly upregulated in NPC tissues and cell lines. Furthermore, HOXC13-AS was identified as an independent prognosis factor by Cox regression analyses. Subsequently, functional assay revealed that knockdown of HOXC13-AS impaired cell proliferation, migration, and invasion. Mechanistically, RIP and luciferase reporter analysis confirmed that miR-383-3p was a target of HOXC13-AS. Besides, high mobility group AT-hook 2 (HMGA2) was proved to be a target of miR-383-3p in NPC. Finally, rescue assays demonstrated that HOXC13-AS functioned as a competing endogenous RNAs to enhance the expression of HMGA2 via sponging miR-383-3p. This study suggested that HOXC13-AS exerted oncogenic function in NPC via regulating miR-383-3p/HMGA2 axis, indicating HOXC13-AS may be a potential therapeutic target for patients with NPC.

M2 Macrophage exosomal HOXC13-AS in laryngeal cancer immunity via targeting miR-485-5p/IGF2BP2/PD-L1.

This study investigates the role of M2-exo-mediated HOXC13-AS in laryngeal squamous cell carcinoma (LSCC) by examining its transmission to tumor microenvironment (TME) macrophages. Exosomes from M2 macrophages were isolated and characterized using transmission electron microscopy, nanoparticle tracer analysis and western blot. Expression of HOXC13-AS, miR-485-5p, IGF2BP2, and PD-L1 was analyzed. Different interventions on LSCC cell function and immune escape were detected using molecular biological techniques. The study found that elevated HOXC13-AS were present in LSCC, and M2-exo expression was significantly increased in LSCC cells. Silencing HOXC13-AS in M2-exo inhibited LSCC malignant progression and immune escape in vivo and in vitro. M2-exo-mediated HOXC13-AS also regulated IGF2BP2 expression, impacting cellular biological function and immune escape process. The study concludes that M2-exo-mediated HOXC13-AS promotes LSCC malignancy and immune escape.

HOXC13-AS Induced Extracellular Matrix Loss via Targeting miR-497-5p/ADAMTS5 in Intervertebral Disc.

Background/Aims: LncRNAs are a new modulator in the development of intervertebral disc degeneration. However, the functional role and mechanism of HOXC13-AS in intervertebral disc degeneration remain unclear. Methods: qRT-PCR analysis was performed to measure the relative expression levels of HOXC13-AS and miR-497-5p, and the levels of IL-1ß, IL-6, and TNF-α in the medium supernatant were analyzed by ELISA. The related mechanism between HOXC13-AS and miR-497-5p was detected by luciferase assays. Results: The results revealed that TNF-α and IL-1ß induced HOXC13-AS expression in NP cells. HOXC13-AS was overexpressed in IDD specimens compared to control specimens, and higher expression of HOXC13-AS was correlated with high Pfirrmann scores. Ectopic expression of HOXC13-AS promoted MMP-3 and ADAMTS4 and inhibited aggrecan and collagen II expression in NP cells. Furthermore, overexpression of HOXC13-AS increased the expression of inflammatory cytokines, including IL-1ß, IL-6, and TNF-α. Our results demonstrated that TNF-α and IL-1ß induced ADAMTS5 expression and suppressed miR-497-5p expression. miR-497-5p was downregulated in IDD specimens compared to control specimens, and the lower expression of miR-497-5p was correlated with high Pfirrmann scores. The miR-497-5p level was negatively proportional to HOXC13-AS expression in IDD specimens. Luciferase analysis data indicated that ADAMTS5 was a direct target gene of miR-497-5p. HOXC13-AS induced inflammatory cytokine expression and ECM degradation by modulating miR-497-5p/ADAMTS5. Conclusion: HOXC13-AS may be a treatment target for IDD.

LINC00958 and HOXC13-AS as key candidate biomarkers in head and neck squamous cell carcinoma by integrated bioinformatics analysis.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor with a strong tendency for metastasis and recurrence. Finding effective biomarkers for the early diagnosis of HNSCC is critical for the early treatment and prognosis of patients. METHODS: RNA sequencing data including long non-coding RNAs (lncRNAs), messenger RNA (mRNAs) and microRNAs (miRNAs) of 141 HNSCC and 44 adjacent normal tissues were obtained from the TCGA. Differentially expressed genes were analyzed using the R package DESeq. GO terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. A competing endogenous RNAs (ceRNA) network was constructed. The most differentially expressed genes in the main ceRNA network were chosen for nasopharyngeal carcinoma (NPC) cell lines and NPEC2 Bmi-1 cell line verification. A receiver operating characteristic (ROC) curve was constructed for 141 specimens of HNSCC tissues from 44 control samples. RESULTS: In our study, 79 HNSCC-associated abnormally expressed lncRNAs , 86 abnormally expressed miRNAs and 324 abnormally expressed mRNAs were identified. The public microarray results showed that LINC00958 and HOXC13-AS expression levels were upregulated in HNSCC tissues compared with the adjacent normal tissues in this study (p < 0.0001). LINC00958 and HOXC13-AS expression levels in NPC cell lines were higher than those in the NPEC2 Bmi-1 cell line (p < 0.05). The results showed that the area under the ROC curve (AUC) of LINC00958 reached up to 0.906 at a cutoff value of 7.96, with a sensitivity and specificity of 80.85% and 90.91%, respectively. The AUC of HOXC13-AS reached up to 0.898 at a cutoff value of 0.695, with sensitivity and specificity values of 86.23% and 83.78%, respectively. CONCLUSION: The current study indicates that LINC00958 and HOXC13-AS are new candidate diagnostic biomarkers for HNSCC patients.

HOXC13-AS accelerates cell proliferation and migration in oral squamous cell carcinoma via miR-378g/HOXC13 axis.

Oral squamous cell carcinoma (OSCC) is an aggressive cancer type in head and neck. A number of long non-coding RNAs (lncRNAs) are discovered to serve regulatory roles in OSCC. HOXC13 antisense RNA (HOXC13-AS) has been proved to behave as a tumor-facilitator in nasopharyngeal carcinoma, but its regulatory role in OSCC has never been investigated. In this study, GEPIA indicated that HOXC13-AS and its neighbor gene HOXC13 were upregulated in HNSC samples, and we consistently unveiled their upregulation in OSCC tissues and cell lines. Silencing HOXC13-AS abrogated OSCC cell proliferation, migration, and epithelial-to-mesenchymal transition (EMT). Moreover, HOXC13 overexpression rescued the influences of HOXC13-AS silence on OSCC cellular processes and in vivo tumor growth. Mechanistically, HOXC13-AS upregulated HOXC13 expression in OSCC through sequestering miR-378g, which was proved to exert suppressive functions in the malignant behaviors of OSCC cells. Further, HOXC13 was revealed to be positively correlated with HOXC13-AS and negatively with miR-378g in expression in OSCC samples. In sum, our findings suggested that HOXC13-AS functioned as a ceRNA to accelerate the malignant behaviors of OSCC cells via miR-378g/HOXC13 axis, shedding a new light on the lncRNA-targeted treatment for OSCC.

HOXC10 is significantly overexpressed in colorectal cancer.

Colorectal cancer (CRC) is one of the most common types of cancer in world and has a high rate of mortality. The majority of cases of CRC are sporadic; however, factors such as age, a family history of inflammatory diseases, diet, lifestyle and genetics increase the risk. HOX genes and lncRNAs are two classes of genes, and alterations in the expression levels of these genes are significantly associated with numerous different types of cancer. In the present study, the expression levels of HOXC10, HOXC-AS3, HOTAIR, HOXC13 and HOXC13-AS in tumor tissues were compared with normal healthy tissues in patients with CRC. Paired tumor and normal tissues were collected from 39 patients with CRC, and reverse transcription-quantitative PCR was used the expression of HOXC-AS3, HOXC13 and HOXC10 in the tumor tissues compared with the respective normal tissues. Expression of these genes were increased in the tumor tissues compared with normal tissues; however, the difference was only significant for HOXC10. Additionally, there was a strong and significant correlation between the expression of HOTAIR and HOXC13, a moderate and significant correlation between the expression of HOTAIR and HOXC13-AS, and between HOXC13 and HOXC13-AS genes. The expression of HOXC10 was significantly higher in tumor tissues compared with the normal tissues; whereas the upregulation of HOXC-AS3 and HOXC13 were not significant. Only the correlation between the expression of HOTAIR and HOXC13 was strong and significant. As HOXC10 expression was significantly upregulated in the tumor tissues relative to normal tissues, it may serve as a biomarker for the diagnosis of CRC and as a potential therapeutic target.

HOXC13-AS-miR-122-5p-SATB1-C-Myc feedback loop promotes migration, invasion and EMT process in glioma.

PURPOSE: Differentially expressed long non-coding ribonucleic acids (lncRNAs) have been reported as a key factor of glioma carcinogenesis, but the underlying mechanism involved is still unknown. MATERIALS AND METHODS: In the present study, lncRNA HOXC13 antisense RNA (HOXC13-AS) was identified as a potential oncogene in glioma, and Western blotting, wound healing and Transwell assays were carried out to explore the effects of HOXC13-AS on the epithelial-mesenchymal transition (EMT) process as well as the migration and invasion of glioma cells. RESULTS: A further mechanistic study showed that HOXC13-AS sponged miR-122-5p to indirectly regulate SATB1 expression and affect the EMT process via the Wnt/ß-catenin pathway. Meanwhile, the promoter activity was significantly increased via c-Myc, a key factor of the Wnt/ß-catenin pathway, thus forming a positive HOXC13-AS-miR-122-5p-SATB1-c-Myc feedback loop to drive the malignant behavior in glioma. DISCUSSION: This study evidences the constitutive HOXC13-AS-miR-122-5p-SATB1-c-Myc feedback loop and provides a potential therapeutic target for glioma treatment.