LncRNA HOXA-AS2 Activates the Notch Pathway to Promote Cervical Cancer Cell Proliferation and Migration

Wu, Qiyan; Lu, Shentao; Zhang, Li; Zhao, Lingjun

doi:10.1007/s43032-021-00626-y

Cited by 17 publications

(13 citation statements)

References 43 publications

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“…In colorectal cancer, Ding et al found that silencing HOXA-AS2 could promote apoptosis, inhibit the proliferation and migration by binding to EZH2/LSD1, and upregulated HOXA-AS2 is positively correlated with larger tumor size, advanced tumor stage and early lymph node metastasis. Wu Q et al reported that HOXA-AS2 may promote the cell proliferation and migration of cervical cancer cells by modulating the Notch pathway (34). Gao Y et al identified that HOXA-AS2 can play a role in glioblastoma cell viability, invasion, migration, and vasculogenic mimicry by interacting with EFGR via sponging miR-373 (59).…”

Section: Discussionmentioning

confidence: 99%

“…HOXA-AS2 is a 1048-bp long noncoding RNA located on human chromosome 7p15.2 between the HOXA3 and HOXA4 genes in the HOXA cluster ( 11 ). In recent years, an increasing number of publications have shown that HOXA-AS2 is highly expressed in diverse malignancies, including oral squamous cell carcinoma ( 12 , 13 ), nasopharyngeal carcinoma ( 14 ), thyroid cancer ( 15 , 16 ), breast cancer ( 17 , 18 ), lung cancer ( 19 – 22 ), gallbladder carcinoma ( 23 ), gastric cancer ( 24 , 25 ), hepatocellular carcinoma ( 26 , 27 ), pancreatic cancer ( 28 ), colorectal cancer ( 29 ), bladder cancer ( 30 ), prostate cancer ( 31 ), ovarian cancer ( 32 ), endometrial cancer ( 33 ), cervical cancer ( 34 , 35 ), osteosarcoma ( 36 , 37 ) and glioblastoma ( 38 ). Cell function tests showed that high HOXA-AS2 expression can promote the proliferation and invasion of cancer cells, inhibit apoptosis, and affect the cancer cell cycle ( 21 , 32 ).…”

Section: Introductionmentioning

confidence: 99%

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HOXA-AS2 may predict the prognosis of solid tumors among Chinese patients: A meta-analysis and bioinformatic analysis

Wang

Zhang²,

Deng³

et al. 2022

Front. Oncol.

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BackgroundHOXA cluster antisense RNA 2 (lncRNA HOXA-AS2) is a long noncoding RNA (lncRNA) that aberrantly expressed in various cancers and is closely associated with cancer progression. To overcome the limitation of small sample sizes that are inherent to single studies, a meta-analysis was conducted to explore the relationship between the expression level of HOXA-AS2 and cancer prognosis.MethodsCorrelational studies were retrieved by searching the databases of PubMed, Embase and Web of Science (up to August 10, 2022). The survival and prognosis data included overall survival (OS), and clinical parameters were gathered and analyzed.ResultsEighteen publications with 1181 patients who were diagnosed with solid tumors were ultimately included. The results showed that, compared with patients with low HOXA-AS2 expression, patients with high HOXA-AS2 expression tended to have poorer overall survival (OS) (HR= 2.52, 95% CI 1.87-3.38, P < 0.01) and shorter disease-free survival (DFS) (HR=7.19, 95% CI 3.20-16.17, P < 0.01). In addition, elevated HOXA-AS2 expression indicated a larger tumor size (OR =2.43, 95% CI 1.53–3.88,P < 0.01), more advanced TNM stage (OR=3.85, 95% CI 2.79-5.31, P < 0.01), earlier lymph node metastasis (LNM) (OR = 4.41, 95% CI 3.05-6.39, P < 0.01) and distant metastasis (DM) (OR= 2.96, 95% CI 1.87-4.7, P < 0.01). Furthermore, HOXA-AS2 expression was notassociated with age (OR=1.15, 95% CI 0.90-1.47), gender (OR=1.16, 95% CI 0.89-1.53), or tumor differentiation (OR=1.21, 95% CI 0.56-2.63). Moreover, aberrant HOXA-AS2 expression was related to drug sensitivity in various types of cancers.ConclusionThe overexpression of HOXA-AS2 predicted poor cancer prognosis in the Chinese population, including poor OS, DFS, TNM, LNM, and DM. HOXA-AS2 could serve as a promising prognostic biomarker and therapeutic target.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022352604.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HOXA-AS2 may predict the prognosis of solid tumors among Chinese patients: A meta-analysis and bioinformatic analysis

Wang

Zhang²,

Deng³

et al. 2022

Front. Oncol.

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“…Then, detection of lncRNA FLVCR1-AS1 in the cytoplasmic and nuclear RNA of HeLa cells was via adopting reverse transcription quantitative polymerase-chain reaction (RT-qPCR). Adoption of U6 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was as nuclear and cytoplasmic control [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

LncRNA FLVCR1-AS1 mediates miR-23a-5p/SLC7A11 axis to promote malignant behavior of cervical cancer cells

Zhou

Zhao

et al. 2022

Bioengineered

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Cervical cancer (CC) is the most common gynecological malignant tumor in the world. Long non-coding RNA (lncRNAs) plays an important role in cell activities of various cancers including CC. This study aims to reveal the biological function of FLVCR1-AS1 in CC and clarify its possible mechanism of action. The findings suggest that the expression of FLVCR1-AS1 was elevated in CC tissues and cell lines, and that high expression of FLVCR1-AS1 was associated with poor prognosis of CC patients. In addition, knockdown of FLVCR1-AS1 could inhibit the proliferation and migration, invasion and epithelial–mesenchymal transformation (EMT) of CC cells, as well as accelerating apoptosis, to inhibit the development of CC. In addition, via the dual-luciferase reporting assay and RIP assay were confirmed that FLVCR1-AS1 acted as a competitive endogenous RNA to inhibit the expression of microRNA (miR)-23a-5p, and miR-23a-5p targeted the 3’-untranslated region site of Solute carrier family 7 member 11 (SLC7A11) and negatively regulated the expression of SLC7A11. Functional rescue experiments showed that miR-23a-5p inhibitors reversed the inhibitory effect of FLVCR1-AS1-silencing on proliferation, EMT, migration and invasion, and the promoting impact of apoptosis of CC cells. In addition, SLC7A11 rescued the effect of miR-23a-5p overexpression on progression of CC cells. In conclusion, FLVCR1-AS1 is involved in the malignant phenotype of CC cells through miR-23a-5p/SLC7A11 axis, which may provide a beneficial direction for the treatment of CC.

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“…HOXA1 has been reported to play a crucial role in multiple biological processes and can mediate gene expression and cell differentiation [29,30]. In addition, HOXA1 could be regulated by the AKT/mTOR signalling pathway and the Notch1 signalling pathway [31,32]. MAML3 was part of the Notch1-containing ternary complex in vivo [33], and has been reported to act as a transcriptional coactivator of NOTCH2.…”

Section: Downstream Signalling Regulated By Trim32mentioning

confidence: 99%

TRIM32 Deficiency Impairs the Generation of Pyramidal Neurons in Developing Cerebral Cortex

Sun

Chen

Huang

et al. 2022

Cells

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Excitatory-inhibitory imbalance (E/I) is a fundamental mechanism underlying autism spectrum disorders (ASD). TRIM32 is a risk gene genetically associated with ASD. The absence of TRIM32 causes impaired generation of inhibitory GABAergic interneurons, neural network hyperexcitability, and autism-like behavior in mice, emphasizing the role of TRIM32 in maintaining E/I balance, but despite the description of TRIM32 in regulating proliferation and differentiation of cultured mouse neural progenitor cells (NPCs), the role of TRIM32 in cerebral cortical development, particularly in the production of excitatory pyramidal neurons, remains unknown. The present study observed that TRIM32 deficiency resulted in decreased numbers of distinct layer-specific cortical neurons and decreased radial glial cell (RGC) and intermediate progenitor cell (IPC) pool size. We further demonstrated that TRIM32 deficiency impairs self-renewal of RGCs and IPCs as indicated by decreased proliferation and mitosis. A TRIM32 deficiency also affects or influences the formation of cortical neurons. As a result, TRIM32-deficient mice showed smaller brain size. At the molecular level, RNAseq analysis indicated reduced Notch signalling in TRIM32-deficient mice. Therefore, the present study indicates a role for TRIM32 in pyramidal neuron generation. Impaired generation of excitatory pyramidal neurons may explain the hyperexcitability observed in TRIM32-deficient mice.

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LncRNA HOXA-AS2 Activates the Notch Pathway to Promote Cervical Cancer Cell Proliferation and Migration

Cited by 17 publications

References 43 publications

HOXA-AS2 may predict the prognosis of solid tumors among Chinese patients: A meta-analysis and bioinformatic analysis

HOXA-AS2 may predict the prognosis of solid tumors among Chinese patients: A meta-analysis and bioinformatic analysis

LncRNA FLVCR1-AS1 mediates miR-23a-5p/SLC7A11 axis to promote malignant behavior of cervical cancer cells

TRIM32 Deficiency Impairs the Generation of Pyramidal Neurons in Developing Cerebral Cortex

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