UCA1 Overexpression Promotes Hypoxic Breast Cancer Cell Proliferation and Inhibits Apoptosis via HIF-1α Activation

Choudhry, Hani

doi:10.1155/2021/5512156

Cited by 12 publications

(11 citation statements)

References 55 publications

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“…Then, we analyzed the reported functions of the top-ten lncRNAs modulated in 3D cultures. Interestingly, some of the lncRNAs with the highest fold change values, such as RP11-20F24.2, UCA1, LINC00672 (up-regulated); and XIST, CYTOR, LINC00857, MIR4435-2HG (down-regulated), have been previously described as deregulated in different types of human cancers with functions associated to cell growth and proliferation, migration, invasion, and metastasis [ 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ] ( Table 1 and Table 2 ). However, the functions of a number of lncRNAs, such as RP11-206M11.7, RP11-782C8.3, and RP11-425M5.7, among others, remain still unknown.…”

Section: Resultsmentioning

confidence: 99%

Breast Cancer Cells Reprogram the Oncogenic lncRNAs/mRNAs Coexpression Networks in Three-Dimensional Microenvironment

Nuñez‐Olvera

Aguilar-Arnal

Cisneros-Villanueva

et al. 2022

Cells

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Organotypic three-dimensional (3D) cell cultures more accurately mimic the characteristics of solid tumors in vivo in comparison with traditional two-dimensional (2D) monolayer cell models. Currently, studies on the regulation of long non-coding RNAs (lncRNAs) have not been explored in breast cancer cells cultured in 3D microenvironments. In the present research, we studied the expression and potential roles of lncRNAs in estrogen receptor-positive luminal B subtype BT-474 breast cancer cells grown over extracellular matrix proteins-enriched 3D cultures. Global expression profiling using DNA microarrays identifies 290 upregulated and 183 downregulated lncRNAs in 3D cultures relative to 2D condition. Using a co-expression analysis approach of lncRNAs and mRNAs pairs expressed in the same experimental conditions, we identify hundreds of regulatory axes modulating genes involved in cancer hallmarks, such as responses to estrogens, cell proliferation, hypoxia, apical junctions, and resistance to endocrine therapy. In addition, we identified 102 lncRNAs/mRNA correlations in 3D cultures, which were similar to those reported in TCGA datasets obtained from luminal B breast cancer patients. Interestingly, we also found a set of mRNAs transcripts co-expressed with LINC00847 and CTD-2566J3.1 lncRNAs, which were predictors of pathologic complete response and overall survival. Finally, both LINC00847 and CTD -2566J3.1 were co-expressed with essential genes for cancer genetic dependencies, such as FOXA1 y GINS2. Our experimental and predictive findings show that co-expressed lncRNAs/mRNAs pairs exhibit a high degree of similarity with those found in luminal B breast cancer patients, suggesting that they could be adequate pre-clinical tools to identify not only biomarkers related to endocrine therapy response and PCR, but to understand the biological behavior of cancer cells in 3D microenvironments.

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Section: Resultsmentioning

confidence: 99%

Breast Cancer Cells Reprogram the Oncogenic lncRNAs/mRNAs Coexpression Networks in Three-Dimensional Microenvironment

Nuñez‐Olvera

Aguilar-Arnal

Cisneros-Villanueva

et al. 2022

Cells

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“…Almost all the experiments revealed the UCA1 overexpression in both cell lines, which significantly promoted their proliferation, invasion, and migration abilities. These functions were accomplished by the sponging effect of UCA1 on several miRNAs, including miR-122-5p [ 24 ], miR-206 [ 33 ], and miR-185-5p [ 37 ], or the upregulation of UCA1 by factors such as TGF-β [ 29 , 34 ], HIF-1a [ 40 ], and macrophages [ 41 ]. Nevertheless, there were two studies demonstrating that MCF7 and T47D cells exhibited lower UCA1 levels than the normal BC cells [ 28 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…The MDA-MB-468 and HCC1937 cells also displayed decreased UCA1 levels, after their exposure to another tumor suppressor, ARID1A [ 26 , 32 ]. In one study, the triple-negative MDA-MB-436 and BT549 cells exhibited significantly more elevated UCA1 expression compared to the MCF7 and MDA-MB-231 cells, while another study showed the BT-20 and MDA-MB-468 cells to overexpress UCA1 after being exposed to hypoxic conditions [ 34 , 40 ]. The induction of apoptosis resulting from UCA1 downregulation by ARID1A was similarly observed in Her2+ JIMT1 cells, while the Her2+ SKBR3 cells demonstrated significantly increased UCA1 expression in response to hypoxic conditions, as well [ 32 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…UCA1 was also overexpressed in the hypoxia-grown SKBR3, MDA-MB-468, MDA-MB-231, and BT474 cells, while the T47D and triple-negative BT-20 cell lines exhibited a lower increase in UCA1. Finally, the tissue analysis demonstrated that BC specimens expressed UCA1 in higher levels compared to the healthy tissues [ 40 ].…”

Section: The Role Of Uca1 In Bc Oncogenesis Proliferation and Invasionmentioning

confidence: 99%

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The Role of Urothelial Cancer-Associated 1 in Gynecological Cancers

Nousiopoulou,

Vrettou,

Damaskos

et al. 2024

CIMB

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Gynecological cancers (GC) represent some of the most frequently diagnosed malignancies in women worldwide. Long-non-coding RNAs (lncRNAs) are regulatory RNAs increasingly being recognized for their role in tumor progression and metastasis in various cancers. Urothelial cancer-associated 1 (UCA1) is a lncRNA, first found deregulated in bladder cancer, and many studies have exposed its oncogenic effects in more tumors since. However, the role of UCA1 in gynecological malignancies is still unclear. This review aims to analyze and define the role of UCA1 in GC, in order to identify its potential use as a diagnostic, prognostic, or therapeutic biomarker of GC. By employing the search terms “UCA1”, “breast cancer”, “endometrial cancer”, “ovarian cancer”, “cervical cancer”, “vaginal cancer”, and “vulvar cancer” in the PubMed database for the literature review, we identified a total of sixty-three relevant research articles published between 2014 and 2024. Although there were some opposing results, UCA1 was predominantly found to be upregulated in most of the breast, endometrial, ovarian, cervical, and vulvar cancer cells, tissue samples, and mouse xenograft models. UCA1 overexpression mainly accounts for enhanced tumor proliferation and increased drug resistance, while also being associated with some clinicopathological features, such as a high histological grade or poor prognosis. Nonetheless, no reviews were identified about the involvement of UCA1 in vaginal carcinogenesis. Therefore, further clinical trials are required to explore the role of UCA1 in these malignancies and, additionally, examine its possible application as a target for upcoming treatments, or as a novel biomarker for GC diagnosis and prognosis.

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“…In breast cancer cell lines, the expression of lncRNA UCA1 was found to be significantly increased under hypoxic conditions, and the proliferative and anti-apoptotic abilities of breast cancer cells were also increased. After HIF-1α was silenced, the level of UCA1 reduced dramatically, indicating that the expression of UCA1 was carried out in a HIF-1α-dependent manner [ 76 ]. LncRNA UCA1 can bind to miR-143 and block its expression, inducing increased high mobility group box 1 (HMGB1) expression.…”

Section: Hif-1α Can Promote Tumor Emt Progression By Regulating Lncrn...mentioning

confidence: 99%

Regulating the Expression of HIF-1α or lncRNA: Potential Directions for Cancer Therapy

Zhang

Ding

Huang

et al. 2022

Cells

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Previous studies have shown that tumors under a hypoxic environment can induce an important hypoxia-responsive element, hypoxia‑induced factor‑1α (HIF-1α), which can increase tumor migration, invasion, and metastatic ability by promoting epithelial-to-mesenchymal transition (EMT) in tumor cells. Currently, with the deeper knowledge of long noncoding RNAs (lncRNAs), more and more functions of lncRNAs have been discovered. HIF-1α can regulate hypoxia-responsive lncRNAs under hypoxic conditions, and changes in the expression level of lncRNAs can regulate the production of EMT transcription factors and signaling pathway transduction, thus promoting EMT progress. In conclusion, this review summarizes the regulation of the EMT process by HIF-1α and lncRNAs and discusses their relationship with tumorigenesis. Since HIF-1α plays an important role in tumor progression, we also summarize the current drugs that inhibit tumor progression by modulating HIF-1α.

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UCA1 Overexpression Promotes Hypoxic Breast Cancer Cell Proliferation and Inhibits Apoptosis via HIF-1α Activation

Cited by 12 publications

References 55 publications

Breast Cancer Cells Reprogram the Oncogenic lncRNAs/mRNAs Coexpression Networks in Three-Dimensional Microenvironment

Breast Cancer Cells Reprogram the Oncogenic lncRNAs/mRNAs Coexpression Networks in Three-Dimensional Microenvironment

The Role of Urothelial Cancer-Associated 1 in Gynecological Cancers

Regulating the Expression of HIF-1α or lncRNA: Potential Directions for Cancer Therapy

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