Oncogene In Breast Cancer Research Articles

NR2F1-AS1 Acts as an Oncogene in Breast Cancer by Competitively Binding with miR-641.

Background Long noncoding RNA (lncRNA) NR2F1-AS1 has been previously reported to be dysregulated in human cancers and implicated in the tumorigenesis and development of tumors. In this research, we detected the expression level and biological function of NR2F1-AS1 in breast cancer (BC). Methods The expression of NR2F1-AS1 in BC tissues and cell lines was determined by qRT-PCR analysis. The associations of NR2F1-AS1 expression with clinical characteristics and survival rate of BC patients were also analyzed. Cell proliferation, migration, and invasion were measured by the CCK-8 and Transwell assay. Results The results revealed that the total survival time of BC patients with high NR2F1-AS1 expression was lower than that of BC patients with low NR2F1-AS1 expression. Moreover, functional experiments demonstrated that knockdown of NR2F1-AS1 inhibited BC cell viability, migration, and invasion abilities, whereas overexpression of NR2F1-AS1 had the opposite effect. Mechanistic investigation revealed that NR2F1-AS1 can competitively bind with microRNA-641 (miR-641) in BC. These results revealed that NR2F1-AS1 functioned as an oncogene by sponging miR-641 expression in BC cell progression. Moreover, miR-641 was negatively correlated with NR2F1-AS1 in BC tissues. Conclusion Hence, NR2F1-AS1 was found to act as an oncogene in breast cancer by suppressing miR-641. We suggested that NR2F1-AS1 could be a potential biomarker for BC diagnosis and therapy.

SEC61G regulates breast cancer cell proliferation and metastasis by affecting the Epithelial-Mesenchymal Transition.

Breast cancer is a common malignant tumor for women and its incidence has increased constantly in recent decades. The underlying molecular means of breast tumorigenesis endure uncertain. With the sequencing expertise, we found that the SEC61G gene is overexpressed in tumor tissues. However, the biological function of SEC61G in breast malignancy has yet to be determined.We investigated the SEC61G expression level, genetic alteration, IHC, immune infiltration, diagnostic value, survival analysis, and functional enrichment analysis by bioinformatics analysis. Then, vitro experiments were done. We investigated that SEC61G was greater in breast cancer tissues related to adjacent non-tumor tissues through qRT-PCR. We performed proliferation, colony formation, migration, invasion assays, and EMT-related phenotype to determine the specific biological functions of SEC61G in breast cancer cell lines (MDA-MB-231, BT-549) transfected with small interfering RNA.SEC61G expression and exon expression were higher in the tumor while the level of SEC61G methylation was higher in normal tissues. The expression level of SEC61G was connected with immune infiltration and survival and was an effective diagnostic and prognostic indicator. The functional enrichment analysis of SEC61G prompted that SEC61G might play a tumor-promoting role via the EMT pathway. In vitro experiments indicated that knocking down SEC61G considerably impaired the colony formation, cck-8, migration, and invasion, and induced apoptosis of the breast cancer cell lines. The vitro experiments also indicated that ectopic expression of SEC61G could influence EMT.This study revealed that SEC61G plays vital tumorigenic functions and acts as a novel oncogene in breast cancer.

TBX1 functions as a putative oncogene of breast cancer through promoting cell cycle progression.

We have previously identified a genetic variant, rs34331122 in the 22q11.21 locus, as being associated with breast cancer risk in a genome-wide association study. This novel variant is located in the intronic region of the T-box transcription factor 1 (TBX1) gene. Cis-expression quantitative trait loci analysis showed that expression of TBX1 was regulated by the rs34331122 variant. In the current study, we investigated biological functions and potential molecular mechanisms of TBX1 in breast cancer. We found that TBX1 expression was significantly higher in breast cancer tumor tissues than adjacent normal breast tissues and increased with tumor stage (P < 0.05). We further knocked-down TBX1 gene expression in three breast cancer cell lines, MDA-MB-231, MCF-7 and T47D, using small interfering RNAs and examined consequential changes on cell oncogenicity and gene expression. TBX1 knock-down significantly inhibited breast cancer cell proliferation, colony formation, migration and invasion. RNA sequencing and flow cytometry analysis revealed that TBX1 knock-down in breast cancer cells induced cell cycle arrest in the G1 phase through disrupting expression of genes involved in the cell cycle pathway. Furthermore, survival analysis using the online Kaplan-Meier Plotter suggested that higher TBX1 expression was associated with worse outcomes in breast cancer patients, especially for estrogen receptor-positive breast cancer, with HRs (95% CIs) for overall survival (OS) and distant metastasis free survival (DMFS) of 1.5 (1.05-2.15) and 1.55 (1.10-2.18), respectively. In conclusion, our results suggest that the TBX1 gene may act as a putative oncogene of breast cancer through regulating expressions of cell cycle-related genes.

Elevated EDAR signalling promotes mammary gland tumourigenesis with squamous metaplasia

Ectodysplasin A receptor (EDAR) is a death receptor in the Tumour Necrosis Factor Receptor (TNFR) superfamily with roles in the development of hair follicles, teeth and cutaneous glands. Here we report that human Oestrogen Receptor (ER) negative breast carcinomas which display squamous differentiation express EDAR strongly. Using a mouse model with a high Edar copy number, we show that elevated EDAR signalling results in a high incidence of mammary tumours in breeding female mice. These tumours resemble the EDAR-high human tumours in that they are characterised by a lack of oestrogen receptor expression, contain extensive squamous metaplasia, and display strong β-catenin transcriptional activity. In the mouse model, all of the tumours carry somatic deletions of the third exon of the CTNNB1 gene that encodes β-catenin. Deletion of this exon yields unconstrained β-catenin signalling activity. We also demonstrate that β-catenin activity is required for transformed cell growth, showing that increased EDAR signalling creates an environment in which β-catenin activity can readily promote tumourigenesis. Together, this work identifies a novel death receptor oncogene in breast cancer, whose mechanism of transformation is based on the interaction between the WNT and Ectodysplasin A (EDA) pathways.

Metabotropic Glutamate Receptor 8 Is Regulated by miR-33a-5p and Functions as an Oncogene in Breast Cancer.

It has been reported that glutamate metabotropic receptor 8 (GRM8) is closely implicated in the progression of human neuroblastoma, lung cancer, and glioma, but its role in breast cancer remains unknown. Thus, the present study was performed to uncover it. Immunohistochemistry, real-time PCR (RT-PCR), and western blotting experiments were performed to test GRM8 expression levels in tissues and cells. Cell functions were assessed by Cell Count Kit 8 (CCK-8), flow cytometry, wound healing, transwell chambers, and in vivo xenotransplantation experiments. The relationship between miR-33a-5p and GRM8 was evaluated by luciferase gene reporter and western blotting assay. The results showed that GRM8 expression was increased in breast cancer tissues and cells, which was closely associated with lower overall survival rate. Ectopic expression of GRM8 significantly enhanced cell growth, migration, and invasion and tumorigenesis and repressed cell apoptosis. In addition, GRM8 was under the negative regulation of miR-33a-5p, which was downregulated in breast cancer tissues and served as a tumor suppressor. Moreover, overexpression of GRM8 abrogated the inhibitive role of miR-33a-5p played in breast cancer. Collectively, this study reveals that GRM8 functions as an oncogene in breast cancer and is regulated by miR-33a-5p.

Conjoint analysis of circulating tumor cells and solid tumors for exploring potential prognostic markers and constructing a robust novel predictive signature for breast cancer

BackgroundDistance metastasis is the leading cause of death for breast cancer patients, and circulating tumor cells (CTCs) play a key role in cancer metastasis. There have been few studies on CTCs at the molecular level due to their rarity, and the heterogeneity of CTCs may provide special information for solid tumor analysis.MethodsIn this study, we used the gene expression and clinical information of single-cell RNA-seq data of CTCs of breast cancer and discovered a cluster of epithelial cells that had more aggressive characteristics. The differentially expressed genes (DEGs) between the identified epithelial cells cluster and others from single-CTCs were selected for further analysis in bulk sequence data of solid breast cancers.ResultsEighteen genes closely related to the specific CTC epithelial phenotype and breast cancer patient prognosis were identified. Among these 18 genes, we selected the GARS gene, which has not been studied in breast cancer, for functional research and confirmed that it may be a potential oncogene in breast cancer. A risk score was established by the 18 genes, and a high-risk score was strongly associated with a high metastasis rate and poor survival prognosis in breast cancer. The high-risk score group was related to a defective immune infiltration environment in breast cancer, and the immune checkpoint therapy response rate was lower in this group. The drug-sensitive analysis shows that the high-risk score patients may be more sensitive to AKT-mTOR and the cyclin-dependent kinase (CDK) pathways drugs than low-risk score patients.ConclusionsOur 18-gene risk score shows good prognostic and predictive values and might be a personalized prognostic marker or therapy guide marker in breast cancer patients.

Regulatory roles of lncRNA PANDAR in breast cancer cell proliferation.

Breast cancer represents the second most deadly malignancy in women, and long noncoding RNAs (lncRNAs) have crucial functions in its development. To investigate effects of the promoter of CDKN1A antisense DNA damage-activated RNA (PANDAR) on epithelial-mesenchymal transition (EMT) in breast cancer cells and their proliferation. lncRNAs potentially regulating the transcriptional activity of the E-cadherin (E-cad, an epithelial cell marker) gene promoter were screened using a dual-luciferase reporter assay. PANDAR was overexpressed in Michigan cancer foundation 7 (MCF-7) breast cancer cells. E-cad and N-cadherin (N-cad, a mesenchymal cell marker) levels were detected by immunoblotting. Cell viability was assessed using a cell counting kit-8. PANDAR and TCONS00068220/LOC105375819 conservatively regulated the promoter activity of E-cad. PANDAR overexpression in MCF-7 inhibited E-cad expression, but upregulated N-cad. The enhanced expression of PANDAR promoted cell proliferation. PANDAR is a key transcriptional repressor of E-cad and has regulatory effects on the promotion of cell proliferation. PANDAR is an oncogene in breast cancer, potentially facilitating the EMT process and promoting cell proliferation.

Long noncoding RNA PVT1 promotes breast cancer proliferation and metastasis by binding miR-128-3p and UPF1

BackgroundMounting evidence supports that long noncoding RNAs (lncRNAs) have critical roles during cancer initiation and progression. In this study, we report that the plasmacytoma variant translocation 1 (PVT1) lncRNA is involved in breast cancer progression.MethodsqRT-PCR and western blot were performed to detect the gene and protein expression. Colony formation would healing and transwell assays were used to detect cell function. Dual-luciferase reporter assay and RNA pull-down experiments were used to examine the mechanisms interaction between molecules. Orthotopic mouse models were established to evaluate the influence of PVT1 on tumor growth and metastasis in vivo.ResultsPVT1 is significant upregulated in breast cancer patients’ plasma and cell lines. PVT1 promotes breast cancer cell proliferation and metastasis both in vitro and in vivo. Mechanistically, PVT1 upregulates FOXQ1 via miR-128-3p and promotes epithelial–mesenchymal transition. In addition, PVT1 binds to the UPF1 protein, thereby inducing epithelial–mesenchymal transition, proliferation and metastasis in breast cancer cells.ConclusionPVT1 may act as an oncogene in breast cancer through binding miR-128-3p and UPF1 and represents a potential target for BC therapeutic development.

Circular RNA circRPPH1 promotes breast cancer progression via circRPPH1-miR-512-5p-STAT1 axis

Breast cancer (BC) is one of the most fatal diseases among women all over the world. Non-coding RNAs including circular RNAs (circRNAs) have been reported to be involved in different aspects during tumorigenesis and progression. In this study, we aimed to explore the biological functions and underlying mechanism of circRPPH1 in BC. Candidate circRNAs were screened in dataset GSE101123 from Gene Expression Omnibus (GEO) database and a differentially expressed circRNA, circRPPH1, was discovered in BC. CircRPPH1 expression was higher in the cancerous tissue compared to paired adjacent tissue. Further in vitro and in vivo experiments indicated that circRPPH1 acted as an oncogene in BC. In addition, circRPPH1 was mainly localized in cytoplasm and played the role of miR-512-5p sponge. By sequestering miR-512-5p from the 3′-UTR of STAT1, circRPPH1 inhibited the suppressive role of miR-512-5p, stabilized STAT1 mRNA in BC and finally affected BC progression. In conclusion, these findings indicated that circRPPH1 acted as an oncogene and regulated BC progression via circRPPH1-miR-512-5p-STAT1 axis, which might provide a potential therapeutic target for BC treatment.

LINC01087 indicates a poor prognosis of glioma patients with preoperative MRI

Long intergenic non-coding RNA 01,087 (LINC01087) has been concerned as an oncogene in breast cancer, while its mechanism in glioma has been little surveyed. Thus, we searched the prognostic value and functional action of LINC01087 in glioma. Glioma patients after preoperative MRI diagnosis were enrolled, and LINC01087, microRNA (miR)-1277-5p, and alkaline ceramidase 3 (ACER3) levels were tested in glioma cancer tissue. The correlation between LINC01087 expression and the survival of patients were analyzed. LINC01087, miR-1277-5p, and ACER3 levels in U251 cells were altered via transfection, and cell malignant phenotypes were monitored. The relationship between miR-1277-5p and LINC01087 or ACER3 was detected. The LINC01087 and ACER3 expression was in up-regulation and the miR-1277-5p expression was in down-regulation in clinical glioma samples. High expression of LINC01087 was associated with poor prognosis of glioma patients with preoperative MRI. LINC01087 silencing restrained tumor malignancy in glioma cells. Mechanistically, LINC01087 directly interacted with miR-1277-5p. ACER3 was a known target of miR-1277-5p. Moreover, rescue assays reveal that miR-1277-5p overexpression (or ACER3 overexpression) reversed the effects of LINC01087 upregulation (or miR-1277-5p upregulation) on glioma cells. LINC01087 has prognostic significance in glioma and silencing LINC01087 deters glioma development through elevating miR-1277-5p to reduce ACER3 expression.

ELK1-induced up-regulation of KIF26B promotes cell cycle progression in breast cancer.

KIF26B is a member of the kinesin superfamily that is up-regulated in various tumors, including breast cancer (BC), which can promote tumor progression. This study aimed to investigate the potential function of KIF26B in BC, and the underlying mechanisms, focusing mainly on cell proliferation. KIF26B expression was examined in BC tissue samples obtained from 99 patients. Then, we performed MTS, EdU and flow cytometry assays to detect cell proliferation, and western blotting to measure the expression of cell cycle-related proteins in MDA-MB-231 and MDA-MB-468 cells following KIF26B knockdown. Promoter analysis was used to study the upstream regulatory mechanism of KIF26B. KIF26B was upregulated in BC tissues. High expression of KIF26B was associated with clinicopathological parameters, such as positive lymph node metastasis, higher tumor grade, and higher proliferative index in BC. Furthermore, knockdown of KIF26B expression inhibited MDA-MB-231 and MDA-MB-468 cell proliferation, arresting cells in the G1 phase of the cell cycle in vitro. Similarly, KIF26B silencing decreased the expression levels of Wnt, β-catenin, and cell cycle-related proteins such as c-Myc, cyclin D1, and cyclin-dependent kinase 4, while increasing the expression of p27. Moreover, ELK1 could bind to the core promoter region of KIF26B and activate its transcription. KIF26B acts as an oncogene in BC by regulating multiple proteins involved in the cell cycle. ELK1 activates KIF26B transcription.

Calmodulin acetylation: A modification to remember

The formation of new memories appears to require alterations in the shape and strength of synapses within the hippocampus, yet our knowledge of the molecular mechanisms underlying these changes remains incomplete. Zhang and colleagues provide new understanding of memory formation by uncovering the lysine acetyltransferase SRC3 as the key driver of the novel posttranslational modification of calmodulin (CaM) acetylation, which regulates CaM's activity and subsequent activation of CaMKII. This new pathway is demonstrated to be both necessary and sufficient for CA3→CA1 synapse long-term potentiation (LTP) and fear memory formation, and this approach may act as a blueprint for future investigation of the role of acetylation of other proteins in neuronal functions.

LncRNA ST8SIA6-AS1 facilitates proliferation and invasion in liver cancer by regulating miR-142-3p.

Long non-coding RNA ST8 α-N-acetyl-neuraminide α-2,8-sialyltransferase 6 antisense 1 (ST8SIA6-AS1) has been identified as a novel oncogene in breast cancer. However, its involvement in liver cancer has remained elusive. In the present study, the expression of ST8SIA6-AS1 and microRNA (miR)-142-3p in liver cancer tissues and cell lines was detected by reverse transcription-quantitative PCR. Tumor cell proliferation, migration and invasion assays were performed to determine the biological functions of ST8SIA6-AS1. The targeting interaction between ST8SIA6-AS1 and miR-142-3p predicted by bioinformatics was verified by a luciferase reporter assay and a biotin pulldown assay. The results indicated that ST8SIA6-AS1 was highly expressed in liver cancer tissues and cell lines, and the high expression of ST8SIA6-AS1 in liver cancer tissues was associated with poor prognosis. Knockdown of ST8SIA6-AS1 inhibited the proliferation, metastasis and invasion of liver cancer cells. Mechanistic investigation revealed that ST8SIA6-AS1 sequesters miR-142-3p and negatively regulates miR-142-3p expression in liver cancer cells. Further investigation indicated that the tumor-inhibitory effect of ST8SIA6-AS1 silencing was reversed by miR-142-3p depletion. In conclusion, ST8SIA6-AS1 was indicated to exert an oncogenic function in liver cancer by competitively sponging miR-142-3p.

Circ-EIF6 encodes EIF6-224aa to promote TNBC progression via stabilizing MYH9 and activating the Wnt/beta-catenin pathway

The protein-coding ability of circular RNAs (circRNAs) has recently been a hot topic, but the expression and roles of protein-coding circRNAs in triple-negative breast cancer (TNBC) remain uncertain. By intersecting circRNA sequencing data from clinical samples and cell lines, we identified a circRNA, termed circ-EIF6, which predicted a poorer prognosis and correlated with clinicopathological characteristics in a cohort of TNBC patients. Functionally, we showed that circ-EIF6 promoted the proliferation and metastasis of TNBC cells invitro and invivo. Mechanistically, we found that circ-EIF6 contains a 675-nucleotide (nt) open reading frame (ORF) and that the-150-bp sequence from ATG functioned as an internal ribosome entry site (IRES), which is required for translation initiation in 5' cap-independent coding RNAs. circ-EIF6 encodes a novel peptide, termed EIF6-224 amino acid (aa), which is responsible for the oncogenic effects of circ-EIF6. The endogenous expression of EIF6-224aa was further examined in TNBC cells and tissues by specific antibody. Moreover, EIF6-224aa directly interacted with MYH9, an oncogene in breast cancer, and decreased MYH9 degradation by inhibiting the ubiquitin-proteasome pathway and subsequently activating the Wnt/beta-catenin pathway. Our study provided novel insights into the roles of protein-coding circRNAs and supported circ-EIF6/EIF6-224aa as a novel promising prognostic and therapeutic target for tailored therapy in TNBC patients.

Exosome miR-134-5p restrains breast cancer progression via regulating PI3K/AKT pathway by targeting ARHGAP1.

Exosomes has been shown to be involved in the regulation of cancer progression. However, the role of exosome miR-134-5p in breast cancer (BC) progression is unclear. Exosomes were extracted from BC cells (MCF-7 and MDA-MB-231) using differential centrifugation and were observed by transmission electron microscope (TEM). The protein levels of exosome markers, apoptosis markers, Rho GTPase activating protein 1 (ARHGAP1, an important oncogene in BC) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) markers were detected by western blot (WB) assay. Quantitative real-time PCR was used to measure the expression levels of miR-134-5p and ARHGAP1. Cell cycle and apoptosis, colony number, viability, migration, and invasion were determined by flow cytometry, colony formation assay, MTT assay, and transwell assay, respectively. The interaction between miR-134-5p and ARHGAP1 was confirmed using a dual-luciferase reporter assay. Xenograft models were constructed to verify the role of exosome miR-134-5p in BC tumor growth in vivo. MiR-134-5p was lowly expressed in BC cells and in the exosomes of BC cells. Overexpressed exosome miR-134-5p suppressed the proliferation, migration, invasion, and promoted the apoptosis of BC cells. ARHGAP1 was a target of miR-134-5p, and its silencing could inhibit BC progression. In addition, ARHGAP1 overexpression could reverse the negative regulation of miR-134-5p on BC progression. MiR-134-5p could target ARHGAP1 to inhibit the activity of PI3K/AKT pathway. Exosome miR-134-5p overexpression could suppress BC tumor growth via targeting ARHGAP1 in vivo. Exosome miR-134-5p restrained BC progression through regulating ARHGAP1/PI3K/AKT signaling pathway, suggesting that miR-134-5p might be a therapeutic target for BC.

Exosome-mediated transfer of circHIPK3 promotes trastuzumab chemoresistance in breast cancer

Breast cancer (BC) remains a public health dilemma in the world and it is one of the leading causes of death among women. Trastuzumab is a kind of commonly-used drugs in the treatment of BC, which especially can provide substantial benefits for HER2-positive BC. However, its long-time usage results in the emergence of resistance, which cuts down its efficacy in BC and leads to a poorer overall survival rate. Hence, the attempt of this study was to investigate how the drug resistance was enhanced. It has been identified that circHIPK3 could act as an oncogene in BC and promoted cell development through and a series of function assays. However, the underlying regulatory mechanism of circHIPK3 is not well established in trastuzumab resistance to date. Furthermore, we found the functional role of exosomes in trastuzumab chemoresistance and discovered that exosomes derived from trastuzumab-resistant cells could enhance the drug resistance of trastuzumab-sensitive cells. In last decades, competing endogenous RNA (ceRNA) has been a hot topic to investigate potential mechanism in cells. We subsequently performed mechanism experiments and rescue assays to verify circHIPK3 acted as a ceRNA in BC cells. In conclusion, we uncovered the regulatory mechanism by which exosome-transmitted circHIPK3 could promote trastuzumab chemoresistance of drug-sensitive BC cells.

Exploring the Significance of the Exon 4-Skipping Isoform of the ZNF217 Oncogene in Breast Cancer.

Oncogene alternative splicing events can create distinct functional transcripts that offer new candidate prognostic biomarkers for breast cancer. ZNF217 is a well-established oncogene but its exon 4-skipping isoform (ZNF217-ΔE4) has never been investigated in terms of clinical or biological relevance. Using in silico RNA-seq and RT-qPCR analyses, we demonstrated for the first time the existence of ZNF217-ΔE4 transcripts in primary breast tumors, and a positive correlation between ZNF217-ΔE4 mRNA levels and those of the wild-type oncogene (ZNF217-WT). A pilot retrospective analysis revealed that, in the Luminal subclass, the combination of the two ZNF217 variants (the ZNF217-ΔE4-WT gene-expression signature) provided more information than the mRNA expression levels of each isoform alone. Ectopic overexpression of ZNF217-ΔE4 in breast cancer cells promoted an aggressive phenotype and an increase in ZNF217-WT expression levels that was inversely correlated with DNA methylation of the ZNF217 gene. This study provides new insights into the possible role of the ZNF217-ΔE4 splice variant in breast cancer and suggests a close interplay between the ZNF217-WT and ZNF217-ΔE4 isoforms. Our data suggest that a dual signature combining the expression levels of these two isoforms may serve as a novel prognostic biomarker allowing better stratification of breast cancers with good prognosis and aiding clinicians in therapeutic decisions.

Abstract 2406: The essential role of ATP binding to the mitochondrial protein ATAD3A in driving oncogenesis of head and neck squamous cell carcinoma

Abstract Head and neck squamous cell carcinoma (HNSCC) represents only 4% of all cancers in the US, but the adverse impact of this disease on health quality is dramatic. There has been little improvement in HNSCC treatment outcomes in decades, and a better understanding of the molecular biology of HNSCC is urgently needed to facilitate the design of anti-HNSCC therapies. The mitochondrial ATPase family AAA-domain containing protein 3A (ATAD3A) has been demonstrated as an oncogene in breast and lung cancer. However, nothing has been reported regarding its role in HNSCC. We report here that loss of ATAD3A expression inhibits HNSCC cell growth as evidenced by reduced cell proliferation and decreased the ability of colony formation and anchorage-independent growth in soft agar, whereas gain of ATAD3A expression counteracts the observed effects. Overexpression of a Walker A dead mutant of ATAD3A (ATAD3AK358) leads to a suppression in HNSCC cell growth and lipids synthesis, suggesting a potent dominant-negative effect of defective ATP-binding of ATAD3A. In line with the in vitro data, overexpression of ATAD3A facilities tumor growth in an orthotopic mouse model of HNSCC. In contrast, inhibition of ATAD3A function by knockout of ATAD3A or expression of ATAD3AK358 induces significant repression of tumor growth. These findings indicate that the mitochondrial protein ATAD3A plays an oncogenic role in HNSCC, and abrogating its ATP-binding ability may represent a promising regimen for better treatment of patients with HNSCC. Citation Format: Liwei Lang, Tiffany Lam, Alex Chen, Chole Shay, Yong Teng. The essential role of ATP binding to the mitochondrial protein ATAD3A in driving oncogenesis of head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2406.

Tumor protein D52 promotes breast cancer proliferation and migration via the long non-coding RNA NEAT1/microRNA-218-5p axis.

BackgroundBreast cancer is an aggressive disease with high morbidity and mortality rates among women globally. Tumor protein D52 (TPD52) is an oncogene in breast cancer; however, its physiological function remains elusive. This study set out to obtain a deeper understanding of the functions of TPD52 in the pathophysiology of breast cancer by exploring its effects on breast cancer cell proliferation and migration.MethodsBioinformatics analysis was performed to predict the bonding of TPD52 and nuclear paraspeckle assembly transcript 1 (NEAT1) with miR-218-5p. The bonding of TPD52 and NEAT1 with miR-218-5p were verified by luciferase reporter assays. The mRNA expression of TPD52, miR-218-5p or NEAT1 were tested by Rt-qPCR and the protein expression of TPD52 was tested by western blot. Colony formation and EdU assays were carried out to evaluate cell proliferation. Wound healing and Transwell assays were used to evaluate migration.ResultsIn this study, TPD52 was upregulated in breast cancer cells, and silencing of TPD52 repressed the proliferation and migration of breast cancer cells in vitro and in vivo. Further, microRNA (miR)-218-5p reduced the expression level of TPD52, while overexpression of TPD52 attenuated the effects of miR-218-5p mimics on breast cancer cell proliferation and migration. Also, NEAT1 acted as a competitive endogenous sponge of miR-218-5p to downregulate free miR-218-5p levels. It was further observed that TPD52 overexpression recovered the inhibition of breast cancer cell growth and migration caused by NEAT1 downregulation. These results confirmed the functions of NEAT1 in breast cancer and supported the mechanism of the NEAT1/miR-218-5p/TPD52 axis.ConclusionsOur findings highlight the important role of the NEAT1/miR-218-5p/TPD52 axis in breast cancer cell proliferation and migration. This axis may be a potential therapeutic target for breast cancer.

KIF23 promotes triple negative breast cancer through activating epithelial-mesenchymal transition.

KIF23 is a member of kinesin family, recent researches indicate KIF23 plays an important role in the proliferation and migration of malignant cancer cells. While the function and specific molecule mechanism of KIF23 in triple negative breast cancer remains unclear. QRT-PCR and immunohistochemistry were conducted to analyze expression of KIF23 in triple negative breast cancer tissues and paired paracancer tissues. CCK-8 assay, colony formation assay, wound healing assay and transwell assay were applied for exploring phenotype changing of triple negative breast cancer cell lines MDA-MB-231 and BT549 after siRNA-induced knockdown of KIF23. Several bioinformatic databases were used for predicting miRNAs that combing with KIF23 mRNA and verified by dual luciferase reporter assay. Western blot assay was performed to explore downstream signaling pathway of KIF23. KIF23 was overexpressed in triple negative breast cancer, knockdown of KIF23 by siRNA inhibited proliferation and migration of TNBC cell lines MDA-MB-231 and BT549. Mechanistically, knockdown of KIF23 resulted in the suppression of Epithelial-Mesenchymal Transition. Meanwhile, miR-195-5p was downregulated in TNBC, and dual luciferase reporter assay indicated miR-195-5p could combine with 3'UTR of KIF23 thus promoting degradation of KIF23. KIF23 is a potential oncogene in triple negative breast cancer, miR-195-5p could combine with 3'UTR of KIF23. Our study reveals a new sight into triple negative breast cancer.