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FTX sponged miR-335-5p in LUAD. a The location of FTX in LUAD cells was showed by FISH assay. b RNA pull-down assay examined the interaction between FTX and predicted miRNAs. c Binding sites between FTX and miR-335-5p. d MiR-335-5p expression was detected by RT-qPCR in LUAD cell lines and BEAS-2B cell line. e MiR-335-5p expression was detected in sh-FTX transfected LUAD cells. f MiR-335-5p up-regulation efficiency was examined in H1650 and H1975 cells. g Effect of miR-335-5p mimics on FTX expression was tested. h Luciferase activity of FTX-WT/ Mut reporters was measured in LUAD cells transfected with miR-335-5p mimics or NC mimics. **p < 0.01, N.S. showed no significance
Source publication
Background:
Extensive studies revealed that long non-coding RNAs (lncRNAs) could act as a regulator in tumors, including lung adenocarcinoma (LUAD). LncRNA FTX transcript, XIST regulator (FTX) has been reported to regulate the biological behaviors of some cancers. Nevertheless, its functional role and molecular mechanism remain obscure in LUAD. Ou...
Contexts in source publication
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... we deciphered molecular mechanism that FTX involved in LUAD. It has been reported that lncRNA could regulate cancer progression by serving as miRNA sponge in the cytoplasm [9,10]. Thus, we detected the localization of FTX in LUAD cells by FISH assay, and results displayed that FTX was abundantly distributed in LUAD cell cytoplasm (Fig. 2a), giving the potential of ceRNA hypothesis. Using starBase (http://starb ase.sysu. edu.cn), 6 miRNAs were predicted to possess complementary bases on the sequence of FTX. To further filtrate the selection, RNA pull down assay was performed. Results revealed that biotinylated wild-type FTX pulled down miR-335-5p while other miRNAs were ...
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... giving the potential of ceRNA hypothesis. Using starBase (http://starb ase.sysu. edu.cn), 6 miRNAs were predicted to possess complementary bases on the sequence of FTX. To further filtrate the selection, RNA pull down assay was performed. Results revealed that biotinylated wild-type FTX pulled down miR-335-5p while other miRNAs were not affected (Fig. 2b). Besides, the binding site between FTX and miR-335-5p was projected and the mutation was constructed (Fig. 2c). Moreover, we found that miR-335-5p expressed at a low level in LUAD cells (Fig. 2d). To explore the relationship between miR-335-5p and FTX, we tested miR-335-5p expression in sh-FTX transfected cells. Results disclosed that ...
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... to possess complementary bases on the sequence of FTX. To further filtrate the selection, RNA pull down assay was performed. Results revealed that biotinylated wild-type FTX pulled down miR-335-5p while other miRNAs were not affected (Fig. 2b). Besides, the binding site between FTX and miR-335-5p was projected and the mutation was constructed (Fig. 2c). Moreover, we found that miR-335-5p expressed at a low level in LUAD cells (Fig. 2d). To explore the relationship between miR-335-5p and FTX, we tested miR-335-5p expression in sh-FTX transfected cells. Results disclosed that miR-335-5p expression was elevated upon FTX depletion (Fig. 2e). Then, the transfection efficiency of ...
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... RNA pull down assay was performed. Results revealed that biotinylated wild-type FTX pulled down miR-335-5p while other miRNAs were not affected (Fig. 2b). Besides, the binding site between FTX and miR-335-5p was projected and the mutation was constructed (Fig. 2c). Moreover, we found that miR-335-5p expressed at a low level in LUAD cells (Fig. 2d). To explore the relationship between miR-335-5p and FTX, we tested miR-335-5p expression in sh-FTX transfected cells. Results disclosed that miR-335-5p expression was elevated upon FTX depletion (Fig. 2e). Then, the transfection efficiency of miR-335-5p mimics was examined. Results of RTqPCR displayed that miR-335-5p expression ...
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... miR-335-5p was projected and the mutation was constructed (Fig. 2c). Moreover, we found that miR-335-5p expressed at a low level in LUAD cells (Fig. 2d). To explore the relationship between miR-335-5p and FTX, we tested miR-335-5p expression in sh-FTX transfected cells. Results disclosed that miR-335-5p expression was elevated upon FTX depletion (Fig. 2e). Then, the transfection efficiency of miR-335-5p mimics was examined. Results of RTqPCR displayed that miR-335-5p expression achieved an escalation by transfecting miR-335-5p mimics in LUAD cells (Fig. 2f ). Interestingly, we found that the expression of FTX was not affected by up-regulated miR-335-5p (Fig. 2g). To further confirm the ...
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... FTX, we tested miR-335-5p expression in sh-FTX transfected cells. Results disclosed that miR-335-5p expression was elevated upon FTX depletion (Fig. 2e). Then, the transfection efficiency of miR-335-5p mimics was examined. Results of RTqPCR displayed that miR-335-5p expression achieved an escalation by transfecting miR-335-5p mimics in LUAD cells (Fig. 2f ). Interestingly, we found that the expression of FTX was not affected by up-regulated miR-335-5p (Fig. 2g). To further confirm the interaction between FTX and miR-335-5p, luciferase reporter assay was ...
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... was elevated upon FTX depletion (Fig. 2e). Then, the transfection efficiency of miR-335-5p mimics was examined. Results of RTqPCR displayed that miR-335-5p expression achieved an escalation by transfecting miR-335-5p mimics in LUAD cells (Fig. 2f ). Interestingly, we found that the expression of FTX was not affected by up-regulated miR-335-5p (Fig. 2g). To further confirm the interaction between FTX and miR-335-5p, luciferase reporter assay was ...
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... we observed, the transfection of miR-335-5p mimics led to a decreased luciferase activity of FTX-WT vector while no evident changes were seen in FTX-Mut vector (Fig. 2h). Collectively, FTX acted as a sponge of miR-335-5p in ...
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... mice were subcutaneously inoculated with H1650 cells stably transfected with sh-FTX or sh-NC. Images of tumors in sh-FTX and sh-NC groups were exhibited (Additional file 2: Figure S2A). Tumor volume and weight were respectively detected and evaluated. ...
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... 11 of 13 Huo et al. Cancer Cell Int (2020) 20:89 reduced the volume and weight of tumors compared with sh-NC group (Additional file 2: Figure S2B, C). Then we assessed the expression of FTX and found that FTX expression was reduced due to FTX deficiency (Additional file 2: Figure S2D). ...
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... Cell Int (2020) 20:89 reduced the volume and weight of tumors compared with sh-NC group (Additional file 2: Figure S2B, C). Then we assessed the expression of FTX and found that FTX expression was reduced due to FTX deficiency (Additional file 2: Figure S2D). Owing to the accelerative effect of FTX on cell migration and invasion, we determined the role of FTX deficiency in cell metastasis in vivo. ...
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... lung metastasis of mice was significantly hindered in sh-FTX group compared with sh-NC group (Additional file 2: Figure S2E). Finally, western blot assay examined that NUCB2 protein level was restrained under FTX silencing (Additional file 2: Figure S2F). ...
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... lung metastasis of mice was significantly hindered in sh-FTX group compared with sh-NC group (Additional file 2: Figure S2E). Finally, western blot assay examined that NUCB2 protein level was restrained under FTX silencing (Additional file 2: Figure S2F). Therefore, we concluded that FTX promoted LUAD progression through increasing NUCB expression. ...
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Background
Nowadays, the important roles of long non‐coding RNAs (LncRNAs) in lung adenocarcinoma (LAD) is being increasingly recognized. The purpose of this study was to explore the regulatory mechanism of lncRNA ZFAS1 in LAD.
Methods
The expression and function of lncRNA ZFAS1 were assessed by RT‐qPCR, CCK‐8, transwell and dual luciferase report...
Citations
... Therefore, we conclude that the expression of NUCB-2 in tumor tissue and nesfatin-1 in serum may have the potential to serve as risk factors for NPC progression. NUCB-2 is distributed in multiple types of tissues, including adipose tissue, central neuron system, gastrointestinal system and reproductive organs, and has diverse functions in different tissues and cancers due to the distinct physiological features of each tissue and the involved various pathways [16][17][18][19]. Our studies provided evidences that NUCB-2 differentially expressed in NPC cell lines with different differentiation degrees, but not with different metastatic characteristics. ...
... Another investigation found that the AMP-dependent protein kinase (AMPK)/target of rapamycin complex (mTORC) 1 signaling pathway participated in the regulation of NUCB-2-mediated metastasis and EMT [17]. FTX played an oncogenic role in LUAD and contributed to cancer development via targeting miR-335-5p/NUCB-2 axis [18]. In colon cancer, NUCB-2/nesfatin-1 enhanced migration, invasion and EMT through LKB1/AMPK/TORC1/ZEB1 pathways in vitro and in vivo [19]. ...
Purpose
The association of NUCB-2/Nesfatin-1 with nasopharyngeal carcinoma (NPC) remains unclear. We clarified the role of NUCB-2/Nesfatin-1 in the development, progression and diagnosis of NPC.
Materials and methods
In nasopharyngeal carcinoma cell lines (5-8 F, 6-10B, CNE1, CNE2 and NP69), western blotting, MTT, EdU and other techniques were performed to investigate the role of NUCB-2 in nasopharyngeal carcinoma. 70 tissue samples (39 NPC and 31 rhinitis) and 140 serum samples (including NPC, rhinitis, other head and neck tumors and healthy control) were included to explore the expression of NUCB-2 and its metabolite Nesfatin-1 in tissues or serum of patients with nasopharyngeal carcinoma.
Results
NUCB-2 level in NPC tissue was higher than that in rhinitis tissue (P < 0.05). Suppression of NUCB-2 in the NPC cell line CNE2 inhibited proliferation and clone formation of the cells; on the contrary, improvement of NUCB-2 in the NPC cell line CNE1 promoted cell propagation and clone development. An elevated serum level of NUCB-2 in NPC patients was detected, compared to that in patients with other head and neck tumors, rhinitis or healthy donors. Determination of nesfatin-1 combined with EA-IgA, VCA-IgA and Rta-IgG in serum samples for NPC diagnosis reached a sensitivity of 93.6% and a specificity of 94.5%, while the positive and negative predictive value of this diagnostic model was 89.8% and 96.6%, and the accuracy yielded 94.2%.
Conclusion
This study revealed that NUCB-2 could enhance proliferation of NPC cells and NUCB-2/nesfatin-1 has the potential to be a serological marker to aid early diagnosis of nasopharyngeal carcinoma.
... [49]. In another study, elevated expression of FTX exert oncogenic function on lung adenocarcinoma by sequestering miR-335-5p, which modulated NUCB2 expression [61]. Results of experiments in mice models of lung cancer revealed FTX-OE decreased the number of lung tumor nodules, cancer proliferation, tumor mass and volume [49]. ...
... Results of experiments in mice models of lung cancer revealed FTX-OE decreased the number of lung tumor nodules, cancer proliferation, tumor mass and volume [49]. Besides, FTX-silencing was correlated with decrease volume and weight of tumors [61]. ...
Long non-coding RNAs (lncRNAs) are involved the progression of cancerous and non-cancerous disorders via different mechanism. FTX (five prime to xist) is an evolutionarily conserved lncRNA that is located upstream of XIST and regulates its expression. FTX participates in progression of various malignancy including gastric cancer, glioma, ovarian cancer, pancreatic cancer, and retinoblastoma. Also, FTX can be involved in the pathogenesis of non-cancerous disorders such as endometriosis and stroke. FTX acts as competitive endogenous RNA (ceRNA) and via sponging various miRNAs, including miR-186, miR-200a-3p, miR-215-3p, and miR-153-3p to regulate the expression of their downstream target. FTX by targeting various signaling pathways including Wnt/β-catenin, PI3K/Akt, SOX4, PDK1/PKB/GSK-3β, TGF β1, FOXA2, and PPARγ regulate molecular mechanism involved in various disorders. Dysregulation of FTX is associated with an increased risk of various disorders. Therefore, FTX and its downstream targets may be suitable biomarkers for the diagnosis and treatment of human malignancies. In this review, we summarized the emerging roles of FTX in human cancerous and non-cancerous cells.
... Increasing amounts of evidence has shown that abnormally expressed lncRNAs in RCC are crucially involved in cancer development and progression (11)(12)(13)(14). lncRNA FTX is upregulated in adenocarcinoma and gastric cancer, indicating that lncRNA FTX is an oncogene (15,16). He et al (17) report that lncRNA FTX is upregulated in RCC as an oncogene and its knockdown inhibits the migratory and invasive capacities of RCC cells. ...
The present study aimed to explore the role of long non‑coding (lnc)RNA FTX and ubiquitin‑conjugating enzyme E2C (UBE2C) in promoting the progression of renal cell carcinoma (RCC) and the underlying regulatory mechanism. Relative levels of lncRNA FTX, UBE2C, AKT, CDK1 and CDK6 in RCC cell lines were detected by reverse transcription‑quantitative (RT‑q). Expression levels of UBE2C, phosphorylated (p)‑AKT/AKT, p‑CDK1/CDK1 and p‑CDK6/CDK6 in RCC and paracancerous specimens and RCC cells were measured by western blot or immunohistochemistry assay. In addition, the proliferative rate, cell viability, cell cycle progression, migratory rate and invasive rate of RCC cells overexpressing lncRNA FTX by lentivirus transfection were determined by a series of functional experiments, including the colony formation assay, MTT assay, flow cytometry, Transwell assay and wound healing assay. The targeted binding relationship in the lncRNA FTX/miR‑4429/UBE2C axis was validated by dual‑luciferase reporter assay. By intervening microRNA (miR)‑4492 and UBE2C by the transfection of miR‑4429‑mimics or short interfering UBE2C‑2, the regulatory effect of lncRNA FTX/miR‑4429/UBE2C axis on the progression of RCC was evaluated. Finally, a xenograft model of RCC in nude mice was established by subcutaneous implantation, thus evaluating the in vivo function of lncRNA FTX in the progression of RCC. The results showed that lncRNA FTX and UBE2C were upregulated in RCC specimens and cell lines. The overexpression of lncRNA FTX in RCC cells upregulated UBE2C. In addition, the overexpression of lncRNA FTX promoted the cell viability and proliferative, migratory and invasive capacities of RCC cells and accelerated the cell cycle progression. A dual‑luciferase reporter assay validated that lncRNA FTX exerted the miRNA sponge effect on miR‑4429, which was bound to UBE2C 3'UTR. Knockdown of UBE2C effectively reversed the regulatory effects of overexpressed lncRNA FTX on the abovementioned phenotypes of RCC cells. In the xenograft model of RCC, the mice implanted with RCC cells overexpressing lncRNA FTX showed a larger tumor size and higher tumor weight than those of controls, while the in vivo knockdown of UBE2C significantly reduced the size of RCC lesions, indicating the reversed cancer‑promoting effect of lncRNA FTX. Overall, the present study showed that lncRNA FTX was upregulated in RCC and could significantly promote the proliferative, migratory and invasive capacities, enhancing the viability and accelerating the cell cycle progression of RCC cells by exerting the miRNA sponge effect on miR‑4429 and thus upregulating UBE2C. lncRNA FTX and UBE2C are potential molecular biomarkers and therapeutic targets of RCC.
... NUCB2, located on chromosome 11, encodes a neuropeptide that serves important roles in regulating food intake and energy homeostasis [58]. A study confirmed that NUCB2 was a downstream target of miR-335-5p and that high NUCB2 expression was detected in LUAD and functional assay confirmed that NUCB2 played the oncogenic role in LUAD [59]. HLA-DQA1 is one of the MHC Class II family members and locates on chromosome 6p21. ...
As an essential component of the tumor microenvironment, B cells exist in all stages of tumor and exert important roles in anti-tumor immunity and shaping tumor development. We aimed to explore the expression profile of B cell marker genes and construct a prognostic signature based on these genes in Lung adenocarcinoma (LUAD). A total of 1268 LUAD patients from different cohorts were enrolled in this study. We performed an analysis of single-cell RNA-sequencing (scRNA-seq) data from Gene expression omnibus (GEO) database to identify B cell marker genes in LUAD. TCGA database was used to construct signature, and six cohorts from GEO database were used for validation. We also investigated the association between this signature and immunotherapy response. Based on 258 B cell marker genes identified by scRNA-seq analysis, a nine-gene signature was constructed for prognostic prediction in TCGA dataset, which classified patients into high-risk and low-risk groups according to overall survival. The multivariate analysis demonstrated that the signature was an independent prognostic factor. The signature's predictive power was verified in other six independent cohorts and different clinical subgroups. Analysis of immune profiles showed that high-risk groups presented discriminative immune-cell infiltrations and immune-suppressive states. More importantly, risk scores of the signature were closely correlated with PD-L1, tumor mutation burden, neoantigens, and tumor immune dysfunction and exclusion score. Our study proposed a novel prognostic signature based on B cell marker genes for LUAD patients. The signature could effectively indicate LUAD patients’ survival and serve as a predictor for immunotherapy.
... Increasing evidence has demonstrated that lncRNAs and miRNAs were often interacted in cancer biology [27]. FTX also interacts with different miRNAs in different types of human cancer, such as miR-590-5p in colorectal cancer [28], miR-214-5p in osteosarcoma [29], and miR-335-5p in lung adenocarcinoma [30]. In this study, we predicted the potential miRNA targets of FTX using Starbase 3.0, and found that FTX might bind to miR-320a and sponge it. ...
Long non-coding RNA (lncRNA) five prime to Xist (FTX) exerts important functions in human cancer, while its role in retinoblastoma (RB) remains unclear. This study aimed to investigate the role of FTX in RB. The expression levels of FTX were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was evaluated by cell counting kit-8 (CCK-8), 5‐ethynyl‐2′‐deoxyuridine (EdU) staining and colony formation assays. Cell migration and invasion were detected by Transwell assay. The relationship among FTX, microRNA-320a (miR-320a) and with-no-lysine kinase 1 (WNK1) was also investigated. In the present study, we found that the expression levels of FTX were notably elevated in RB tissues and cancer cell lines. Overexpression of FTX exacerbated the aggressive phenotypes (cell proliferation, migration and invasion) of RB cells. Downregulation of miR-320a obviously attenuated the inhibitory effects of knockdown of FTX in RB malignant phenotypes, and knockdown of WNK1 also reversed the impacts of miR-320a inhibitor on malignant phenotypes. In vivo experiments further confirmed that knockdown of FTX efficiently prevents tumor growth in vivo. Our results revealed that FTX promoted RB progression by targeting the miR-320a/WNK1 axis (graphical abstract), suggesting that FTX might be a novel therapeutic target for RB.
... Although early reports indicated that lncRNA FTX might be located in the nucleus, follow-up reports have demonstrated that lncRNA FTX is localized in both the nucleus and the cytoplasm (22,23). Our results indicated that lncRNA FTX is located in the nucleus and cytoplasm of CRC cells, making it possible to interact with miRNA. ...
Background:
Long non-coding RNAs (lncRNAs) have recently been found to be vital regulators of various cancers, including colorectal cancer (CRC). It has been previously reported that the dysregulated expression of lncRNA Five prime to Xist (FTX) is involved in carcinogenesis. However, the role of lncRNA FTX in the progression of CRC is still unclear.
Methods:
Fluorescence in situ hybridization (FISH) was used to detect the expression of lncRNA FTX and miR-214-5p in CRC tissues. Cell Counting Kit-8 assay, transwell assay, wound-healing assay, and proliferation assay were used to explore the function of lncRNA FTX in CRC cells. Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and luciferase reporter assay were used to confirm the relationship between lncRNA FTX and miR-214-5p-jagged canonical Notch ligand 1 (JAG1). We further explored the role of lncRNA FTX in vivo using xenograft tumor assay.
Results:
lncRNA FTX was found to be upregulated in CRC tissues by FISH. The downregulation of endogenous lncRNA FTX expression inhibited CRC cell proliferation, migration, and invasion. Mechanistically, lncRNA FTX sequestered miR-214-5p and thus released its repression on JAG1, driving the malignant progression of CRC.
Conclusions:
These findings give rise to a new perspective, the lncRNA FTX-miR-214-5p-JAG1 regulatory axis, in exploring the cancer-promoting mechanism of lncRNA FTX in CRC.
... 24 NUCB2 is highly expressed in cell lines of lung adenocarcinoma, and its upregulation reverses the inhibitory effect caused by FTX knockdown on the progression of lung adenocarcinoma. 25 Upregulation of NUCB2 promotes cell proliferation, invasion and tumor growth in papillary thyroid cancer. 26 A previous study also showed that miRNAs regulate the biological processes of cancers by targeting NUCB2. ...
... 27 NUCB2 is targeted by miR-335-5p in LUAD cells and promotes the proliferation and migration of LUAD cells. 25 Based on our findings, miR-30a-5p is downregulated in NPC tissues and cell lines. The overexpression of miR-30a-5p suppressed NPC cell proliferation, migration and invasion in vitro and inhibited tumor growth in vivo by downregulating NUCB2, which suggested that the miR-30a-5p/NUCB2 axis may be useful to further explore NPC biology. ...
Background:
Nasopharyngeal carcinoma (NPC) is a malignant head and neck tumor arising in the nasopharynx. MicroRNAs (miRNAs) are elucidated to exert tumor-suppressing function in human cancers. Numerous studies have manifested that miR-30a-5p serves as an anti-oncogene in various cancers.
Objective:
To research the biological function and molecular mechanism of miR-30a-5p in NPC.
Methods:
The morphology of NPC tissues was revealed by H&E staining. Transwell and wound healing assays were applied to investigate the effects of miR-30a-5p on NPC cell migration. The binding interaction between miR-30a-5p and nucleobindin 2 (NUCB2) was identified by luciferase reporter assay. Xenograft nude mice were used to detect the influence of miR-30a-5p on NPC tumor growth.
Results:
MiR-30a-5p was downregulated in NPC tissues and cells. The overexpression ofmiR-30a-5p inhibited proliferation, migration and invasion abilities of NPC cells. Moreover, NUCB2 was revealed to be a downstream target gene of miR-30a-5p, and knockdown of NUCB2 repressed the malignant behaviors of NPC cells and tumor growth. Additionally, rescue experiments revealed that miR-30a-5p suppressed the proliferation, migration and invasion of NPC cells via targeting NUCB2 in vitro. Meanwhile, in vivo assays depicted that NUCB2 overexpression rescued the effects induced by miR-30a-5p upregulation on tumor growth.
Conclusion:
MiR-30a-5p modulates NPC progression by targeting NUCB2. These findings lay a foundation for exploring the clinical treatment of NPC.
... FTX has been reported to play a role in various types of cancer. In lung adenocarcinoma, the expression levels of FTX were upregulated and promoted the progression of the cell lines (27). In addition, FTX targeted miR-342-3p in glioma to accelerate tumor growth and metastasis (28). ...
The dysregulated expression of long non-coding RNA FTX transcript X inactive specific transcript regulator (FTX) has been reported to be involved in the tumorigenesis of multiple cancer types. However, to the best our knowledge, its function and clinical value in thyroid cancer remain unclear. The present study aimed to determine the potential role of FTX in the development and progression of thyroid cancer. Reverse transcription-quantitative PCR analysis revealed that the expression levels of FTX were upregulated in thyroid cancer tissues and cell lines compared with those in normal tissues and cell lines, respectively. Survival analysis demonstrated that patients with upregulated FTX expression had a lower survival rate. Functional experiments revealed that the knockdown of FTX inhibited proliferation, cell cycle progression, migration and invasion, and induced apoptosis in thyroid cancer cells, while FTX overexpression accelerated proliferation, migration and invasion, and alleviated apoptosis in thyroid cancer cells. In addition, FTX knockdown significantly inhibited tumor growth in vivo. Furthermore, in thyroid cancer cells, FTX was identified to positively regulate the expression levels of TGF-β1, which is known to play an important regulatory role in tumor metastasis. In conclusion, the findings of the present study suggested that FTX may accelerate thyroid cancer progression via regulation of cellular activities, including cell proliferation, migration, invasion and apoptosis. Thus, FTX may represent a potential biomarker for the diagnosis, treatment and prognosis of thyroid cancer.
... Vimentin is also known as a marker and agent of the epithelial to mesenchymal transition (EMT) process [84,85]. Surprisingly, previous research suggested that Nucb2 is involved in EMT [41,86]. This Zn 2+ -dependent structural alteration of Nucb2 molecules might be connected with the role of Nucb2 in the tumorigenesis process. ...
Nucleobindin-2 (Nucb2) is a protein that has been suggested to play roles in a variety of biological processes. Nucb2 contains two Ca²⁺/Mg²⁺-binding EF-hand domains separated by an acidic amino acid residue-rich region and a leucine zipper. All of these domains are located within the C-terminal half of the protein. At the N-terminal half, Nucb2 also possesses a putative Zn²⁺-binding motif. In our recent studies, we observed that Nucb2 underwent Ca²⁺-dependent compaction and formed a mosaic-like structure consisting of intertwined disordered and ordered regions at its C-terminal half. The aim of this study was to investigate the impact of two other potential ligands: Mg²⁺, which possesses chemical properties similar to those of Ca²⁺, and Zn²⁺, for which a putative binding motif was identified. In this study, we demonstrated that the binding of Mg²⁺ led to oligomerization state changes with no significant secondary or tertiary structural alterations of Nucb2. In contrast, Zn²⁺ binding had a more pronounced effect on the structure of Nucb2, leading to the local destabilization of its N-terminal half while also inducing changes within its C-terminal half. These structural rearrangements resulted in the oligomerization and/or aggregation of Nucb2 molecules. Taken together, the results of our previous and current research help to elucidate the structure of the Nucb2, which can be divided into two parts: the Zn²⁺-sensitive N-terminal half (consisting of nesfatin-1 and -2) and the Ca²⁺-sensitive C-terminal half (consisting of nesfatin-3). These results may also help to open a new discussion regarding the diverse roles that metal cations play in regulating the structure of Nucb2 and the various physiological functions of this protein.
... miR-199a contributed to the DDP sensitivity of OC through regulating ITGB8 (Cui et al., 2018). miR-512-3p has been shown to have cancer-inhibiting effects in several cancers, such as prostate cancer (Huo et al., 2020), breast cancer (Mohamadzade et al., 2021), and non-small cell lung cancer (Zhu et al., 2015). However, the function of miR-512-3p implicated in the DDP resistance of OC remains largely unclear. ...
Chemoresistance is one of the major obstacles encountered in ovarian cancer (OC) therapy. Long noncoding RNA PART1 has been reported to be involved in the tumorigenesis of several types of cancers. However, the biological role of PART1 in the chemoresistance of OC is still unclear. In this study, it was found that the expression levels of PART1 and CHRAC1 were increased and miR-512-3p expression was decreased in cisplatin (DDP)-resistant OC cell lines. The depletion of PART1 enhanced the DDP sensitivity of DDP-resistant OC cells, as indicated by the inhibition of cell proliferation, migration, and invasion, and promotion of cell apoptosis. In the upstream mechanism exploration, we discovered that PART1 was induced by YY1 transcription factor. Moreover, it was identified that miR-512-3p was a target of PART1, and PART1 regulated the DDP resistance of OC through miR-512-3p. In addition, we screened the candidate genes of miR-512-3p., and confirmed that CHRAC1 was the downstream gene of miR-512-3p. Furthermore, the knockdown of CHRAC1 inhibited proliferation, migration, and invasion, and accelerated apoptosis of DDP-resistant OC cells, which was counteracted after the inhibition of miR-512-3p. Finally, we observed that PART1 regulated the expression of CHRAC1 through miR-512-3p. In conclusion, we demonstrated that YY1-induced PART1 accelerated DDP resistance of OC through miR-512-3p/CHRAC1 axis, suggesting PART1 may be a promising therapeutic target for DDP-resistant OC patients.
