ABSTRACT
BACKGROUND: Endometrial cancer (EC) is the sixth most frequent cancer in women worldwide and has higher fatality rates. The pathophysiology of EC is complex, and there are currently no reliable methods for diagnosing and treating the condition. Long non-coding RNA (lncRNA), according to mounting evidence, is vital to the pathophysiology of EC. HOTAIR is regarded as a significant prognostic indicator of EC. ZBTB7A decreased EC proliferation and migration, according to recent studies, however the underlying mechanism still needs to be clarified. METHODS: The research utilized RT-qPCR to measure HOTAIR expression in clinical EC tissues and various EC cell lines. Kaplan-Meier survival analysis was employed to correlate HOTAIR levels with patient prognosis. Additionally, the study examined the interaction between ZBTB7A and HOTAIR using bioinformatics tools and ChIP assays. The experimental approach also involved manipulating the expression levels of HOTAIR and ZBTB7A in EC cell lines and assessing the impact on various cellular processes and gene expression. RESULTS: The study found significantly higher levels of HOTAIR in EC tissues compared to adjacent normal tissues, with high HOTAIR expression correlating with poorer survival rates and advanced cancer characteristics. EC cell lines like HEC-1 A and KLE showed higher HOTAIR levels compared to normal cells. Knockdown of HOTAIR in these cell lines reduced proliferation, angiogenesis, and migration. ZBTB7A was found to be inversely correlated with HOTAIR, and its overexpression led to a decrease in HOTAIR levels and a reduction in malignant cell behaviors. The study also uncovered that HOTAIR interacts with ELAVL1 to regulate SOX17, which in turn activates the Wnt/ß-catenin pathway, promoting malignant behaviors in EC cells. CONCLUSION: HOTAIR is a critical regulator in EC, contributing to tumor growth and poor prognosis. Its interaction with ZBTB7A and regulation of SOX17 via the Wnt/ß-catenin pathway underlines its potential as a therapeutic target.
Subject(s)
Cell Proliferation , ELAV-Like Protein 1 , Endometrial Neoplasms , RNA, Long Noncoding , SOXF Transcription Factors , Humans , RNA, Long Noncoding/genetics , Female , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Endometrial Neoplasms/metabolism , SOXF Transcription Factors/genetics , SOXF Transcription Factors/metabolism , ELAV-Like Protein 1/metabolism , ELAV-Like Protein 1/genetics , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/pathology , Transcription Factors/genetics , Transcription Factors/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Prognosis , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Cell Movement/genetics , Animals , Mice , Middle Aged , Wnt Signaling Pathway/genetics , AngiogenesisABSTRACT
Accumulating evidence has demonstrated that long noncoding RNAs (lncRNAs) exert essential biological functions in modulating the progression of endometrial carcinoma (EC). HOX transcript antisense intergenetic RNA (HOTAIR) has been widely recognized as a crucial mediator in various tumors, including EC. However, the specific molecular mechanism of HOTAIR in the development of EC remains to be further explored. In the present study, we demonstrated that HOTAIR was significantly upregulated in EC tissues; this was negatively correlated with PTEN but positively correlated with phosphatidylinositol 3-kinase (PI3K) and Akt. Overexpression of HOTAIR promoted proliferation and inhibited apoptosis of EC cells, similar to PTEN knockdown. Additionally, RNA pulldown demonstrated the direct binding relationship between HOTAIR and PTEN. Furthermore, HOTAIR activated the PI3K/Akt pathway to promote EC progression by suppressing PTEN in vivo Taking these results together, we revealed that high expression of HOTAIR promoted cell proliferation and inhibited apoptosis through activating the PI3K/Akt pathway via binding to PTEN, which might provide a prognostic marker and therapeutic target of EC.
Subject(s)
Endometrial Neoplasms/metabolism , PTEN Phosphohydrolase/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Long Noncoding/metabolism , Adult , Aged , Apoptosis/physiology , Cell Line, Tumor , Cell Movement/physiology , Cell Proliferation/physiology , Disease Progression , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Female , Humans , Middle Aged , PTEN Phosphohydrolase/genetics , Phosphorylation , RNA, Long Noncoding/genetics , Signal TransductionABSTRACT
The genome of kiwifruit (Actinidia chinensis) was sequenced previously, the first in the Actinidiaceae family. It was shown to have been affected by polyploidization events, the nature of which has been elusive. Here, we performed a reanalysis of the genome and found clear evidence of 2 tetraploidization events, with one occurring â¼50-57 million years ago (Mya) and the other â¼18-20 Mya. Two subgenomes produced by each event have been under balanced fractionation. Moreover, genes were revealed to express in a balanced way between duplicated copies of chromosomes. Besides, lowered evolutionary rates of kiwifruit genes were observed. These findings could be explained by the likely auto-tetraploidization nature of the polyploidization events. Besides, we found that polyploidy contributed to the expansion of key functional genes, e.g., vitamin C biosynthesis genes. The present work also provided an important comparative genomics resource in the Actinidiaceae and related families.
