Kinesin Family Member 2A Expression Research Articles

Kinesin Family Member-18A (KIF18A) Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma

Background & AimsKinesin family member 18A (KIF18A) is notable for its aberrant expression across various cancer types and its pivotal role is driving cancer progression. In this study, we aim to investigate the intricate molecular mechanisms underlying the impact of KIF18A on the progression of HCC.MethodsWestern blotting assays, a quantitative real-time PCR and immunohistochemical analyses were performed to quantitatively assess KIF18A expression in HCC tissues. We then performed genetic manipulations within HCC cells by silencing endogenous KIF18A using short hairpin RNA (shRNA) and introducing exogenous plasmids to overexpress KIF18A. We monitored cell progression, analyzed cell cycle and cell apoptosis and assessed cell migration and invasion both in vitro and in vivo. Moreover, we conducted RNA-sequencing to explore KIF18A-related signaling pathways utilizing Reactome and KEGG enrichment methods and validated these critical mediators in these pathways.ResultsAnalysis of the TCGA-LIHC database revealed pronounced overexpression of KIF18A in HCC tissues, the finding was subsequently confirmed through the analysis of clinical samples obtained from HCC patients. Notably, silencing KIF18A in cells led to an obvious inhibition of cell proliferation, migration and invasion in vitro. Furthermore, in subcutaneous and orthotopic xenograft models, suppression of KIF18A sgnificantly redudce tumor weight and the number of lung metastatic nodules. Mechanistically, KIF18A appears to facilitate cell proliferation by upregulating MAD2 and CDK1/CyclinB1 expression levels, with the activation of SMAD2/3 signaling contributing to KIF18A-driven metastasis.ConclusionOur study elucidates the molecular mechanism by which KIF18A mediates proliferation and metastasis in HCC cells, offering new insights into potential therapeutic targets.

Circ_SATB2 knockdown inhibits the tumorigenesis of non-small cell lung cancer via miR-760/KIF2A axis.

This study was aimed at exploring the function and underlying mechanism of circ_SATB2 in non-small cell lung cancer (NSCLC). The levels of circ_SATB2, microRNA-760 (miR-760) and Kinesin family member 2a (KIF2A) were determined using quantitative real-time polymerase chain reaction or western blot assay. The proliferation was detected using MTT and colony formation assays. Cell cycle and apoptosis were evaluated by flow cytometry. Transwell assay for migration and invasion and western blot for metastasis-associated proteins were conducted. Dual-luciferase reporter assay was used to analyze the interaction between miR-760 and circ_SATB2 or KIF2A. The effect of circ_SATB2 on NSCLC tumor growth in vivo was studied by xenograft mice model. Circ_SATB2 was upregulated in NSCLC tissues and cells. Circ_SATB2 knockdown caused inhibitory effects on NSCLC cell proliferation and metastasis but accelerated apoptosis. Circ_SATB2 served as a sponge of miR-760 to act in the development of NSCLC. Moreover, miR-760 could target KIF2A, and KIF2A expression was positively regulated by circ_SATB2. Furthermore, KIF2A overexpression neutralized miR-760-mediated inhibition effects on NSCLC cell progression. Besides, circ_SATB2 enhanced NSCLC tumorigenesis by targeting miR-760/KIF2A axis in vivo. Circ_SATB2 was highly expressed and participated in the progression of NSCLC through the modulation of the miR-760/KIF2A axis, suggesting that circ_SATB2 might be a potential biomarker for the diagnosis of NSCLC.

KIF18A interacts with PPP1CA to promote the malignant development of glioblastoma.

Glioblastoma (GBM), which has poor prognosis and low 5-year survival rate, is the most common primary central nervous system malignant tumour in adults. Kinesin family member 18A (KIF18A) plays an important role in multiple tumours and is potential therapeutic target for GBM. Therefore, the present study investigated the role of KIF18A in GBM. The expression level and survival prognosis of KIF18A and protein phosphatase 1 catalytic subunit α (PPP1CA) in GBM patients were analysed using the Chinese Glioma Genome Atlas (CGGA) database. Reverse transcription-quantitative PCR and western blot analysis were applied to measure the expression of KIF18A and PPP1CA in normal and GBM cell lines. KIF18A expression was inhibited through cell transfection with a KIF18A-targeting short hairpin RNA. Cell proliferation was detected with the Cell Counting Kit-8 assay. Flow cytometry was used to detect cell cycle changes. Transwell and wound healing assays were used to measure cell invasion and migration. Western blotting was utilized for the detection of invasion- and migration-related proteins MMP9 and MMP2. Biological General Repository for Interaction Datasets and GeneMANIA databases were used to analyse the interaction between KIF18A and PPP1CA. The correlation between PPP1CA and KIF18A was examined using data from the CGGA database. Immunoprecipitation was used to demonstrate the binding relationship between KIF18A and PPP1CA. PPP1CA was overexpressed using cell transfection technology and its mechanism was further examined. The results demonstrated that KIF18A was upregulated in GBM cells compared with normal microglia HMC3. Compared with that in sh-NC group, silencing of KIF18A reduced cell proliferation, induced G2/M cycle arrest and inhibited the migration and the invasion of A172 GBM cells by interacting with PPP1CA. In conclusion, KIF18A interacted with PPP1CA to promote the proliferation, cycle arrest, migration and invasion of GBM cells.

KIF2A participates in the progression of hepatocellular carcinoma and angiogenesis by interacting with Notch1.

Kinesin family member 2A (KIF2A) serves a vital role in the development of hepatocellular carcinoma (HCC); however, the biological effect of KIF2A on the malignant progression of HCC remains unclear. Therefore, the present study was conducted to systematically determine the biological role of KIF2A in HCC and to better understand the molecular mechanism. The differences of KIF2A expression in HHL-5 normal human hepatocytes and the HCC cell lines Li-7, Huh7 and MHCC97 were assessed by reverse transcription-quantitative PCR and western blotting analysis. Moreover, viability, proliferation, migration and invasion of HCC cells were assessed by performing CCK-8, 5-ethynyl-2'-deoxyuridine staining, wound healing and Transwell assays. Additionally, the tube formation assay was performed to evaluate angiogenesis of HUVECs incubated with the conditioned media of HCC cells in vitro. The interaction between KIF2A and Notch1 was analyzed through co-immunoprecipitation assay. KIF2A was revealed to be highly expressed in HCC cells. KIF2A knockdown suppressed HCC cell proliferation, migration and invasion, and impaired in vitro angiogenesis. Furthermore, it was revealed that KIF2A interacted with Notch1 and positively regulated Notch1 expression. The suppressive effects of KIF2A knockdown on HCC cell proliferation, migration, invasion and in vitro angiogenesis were partially reversed by Notch1 overexpression. Overall, KIF2A may act as an oncogene in HCC via activation of the Notch1 signaling pathway.

Aberrant kinesin family member 2A signifies tumor size and invasion, and may help predict prognosis of patients with papillary thyroid carcinoma.

Kinesin family member 2A (KIF2A) has been reported as an oncogene and potential biomarker for the progression of numerous cancer types; however, its role in papillary thyroid carcinoma (PTC) has remained elusive. The present study aimed to assess KIF2A expression in patients with PTC and explore the potential association between KIF2A, clinicopathological features and the prognosis of PTC. A total of 200 patients with PTC who received surgical resection were retrospectively reviewed. KIF2A expression was detected using immunohistochemistry (IHC) in 200 pairs of carcinoma/para-carcinoma tissues and using reverse transcription-quantitative PCR in 91 pairs of carcinoma/para-carcinoma tissues. Clinical and pathological data, disease-free survival (DFS) and overall survival (OS) rates of all patients were obtained. The results of the present study demonstrated that KIF2A protein and mRNA expression were both elevated in carcinoma tissues compared with those in para-carcinoma tissues. KIF2A protein expression in carcinoma tissues was positively associated with increased tumor size and a higher pathologic tumor-nodes-metastasis (pTNM) stage. However, KIF2A mRNA expression in carcinoma tissues was only associated with an increased pTNM stage and not with any other clinicopathological features. In addition, high levels of KIF2A protein expression in carcinoma tissues led to a poor predicted DFS, but were not associated with OS. Following adjustments using a multivariate Cox regression model, high KIF2A protein expression levels were indicated to be independently associated with a decreased DFS. In conclusion, aberrant KIF2A signifies tumor size and invasion, and may help to predict prognosis in patients with PTC.

Prognostic Biomarker KIF18A and Its Correlations With Immune Infiltrates and Mitosis in Glioma.

Background: Glioma is globally recognised as one of the most frequently occurring primary malignant brain tumours, making the identification of glioma biomarkers critically significant. The protein KIF18A (Kinesin Family Member 18A) is a member of the kinesin superfamily of microtubule-associated molecular motors and has been shown to participate in cell cycle and mitotic metaphase and anaphase. This is the first investigation into the expression of KIF18A and its prognostic value, potential biological functions, and effects on the immune system and mitosis in glioma patients. Methods: Gene expression and clinicopathological analysis, enrichment analysis, and immune infiltration analysis were based on data obtained from The Cancer Genome Atlas (TCGA), with additional bioinformatics analyses performed. Statistical analysis was conducted in R software. Clinical samples were used to evaluate the expression of KIF18A via immunohistochemical staining. In addition, the expression level of KIF18A was validated on U87 cell line. Results: Our results highlighted that KIF18A plays a key role as an independent prognostic factor in patients with glioma. KIF18A was highly expressed in glioma tissues, and KIF18A expression was associated with age, World Health Organization grade, isocitrate dehydrogenase (IDH) status, 1p/19q codeletion, primary therapy outcome, and overall survival (OS). Enrichment analysis revealed that KIF18A is closely correlated with the cell cycle and mitosis. Single sample gene set enrichment analysis (ssGSEA) analysis revealed that KIF18A expression was related to the immune microenvironment. The increased expression of KIF18A in glioma was verified in clinical samples and U87 cell line. Conclusion: The identification of KIF18A as a new biomarker for glioma could help elucidate how changes in the glioma cell and immune microenvironment promote glioma malignancy. With further analysis, KIF18A may serve as an independent prognostic indicator for human glioma.

KIF18A knockdown reduces proliferation, migration, invasion and enhances radiosensitivity of esophageal cancer

Kinesin family member 18A (KIF18A) is significantly overexpressed and is related to the poor prognosis of human cancers. However, the function of KIF18A in esophageal cancer (EC) is still unclear. Human EC cell lines were used in this study. KIF18A expression in human tissues was assessed using Gene Expression Profiling Interactive Analysis 2.0 (GEPIA2). The expressions of KIF18A or IGF2BP3 in EC cells were detected using qRT-PCR or WB. Cells were transfected using si-KIF18A, si-IGF2BP3, and plasmid IGF2BP3. The abilities of proliferation, migration, and invasion were detected by EdU, wound-healing, and transwell assay. The interaction between KIF18A and IGF2BP3 was predicted by starBase v3.0 and studied by RIP and RNA stability assay. Colony formation assay was used to reflect the changes of radiosensitivity in EC cells. KIF18A was upregulated in EC, and KIF18A knockdown inhibited EC cell proliferation, migration, invasion, and radioresistance. The prediction in starBase and RIP assay results showed that KIF18A mRNA could bind to IGF2BP3 protein in EC cells. RNA stability assay was performed to confirm that IGF2BP3 affects mRNA stability of KIF18A. Further studies also showed that IGF2BP3 could positively regulate KIF18A on proliferation, migration, invasion, and radioresistance. Our findings first revealed an oncogenic effect of KIF18A in human EC progression. KIF18A expression was associated with radioresistance of EC cells. The binding relationship between KIF18A and IGF2BP3 might influence the mRNA stability of KIF18A in EC cell lines.

Clinical significance of kinesin family member 2A as a facilitating biomarker of disease surveillance and prognostication in cervical cancer patients.

Cervical cancer is one of the most common and fatal malignancies among females, and biomarkers are essential for assisting in its management. Kinesin family member 2A (KIF2A) has been exhibited to be a potential maker in various cancers; however, its role in cervical cancer has yet to be reported. Therefore, we aimed to assess the expression of KIF2A and its correlation with clinicopathological characteristics as well as survival profile in cervical cancer patients. A hundred and thirty-five cervical cancer patients who underwent simple trachelectomy or radical hysterectomy were retrospectively analyzed. Tumor tissues and paired adjacent tissues were acquired, in which KIF2A mRNA and protein expressions were determined by reverse transcription quantitative polymerase chain reaction and immunohistochemistry assay, respectively. Disease-free survival (DFS) and overall survival (OS) were documented with a median follow-up duration of 28.0months. KIF2A protein (P < 0.001) and mRNA (P < 0.001) expressions were both upregulated in tumor tissues compared to paired adjacent tissues in cervical cancer patients. In addition, tumor tissue KIF2A protein and mRNA expressions were positively associated with lymph node metastasis (P = 0.025 and P = 0.010, respectively) and FIGO stage (P = 0.022 and P = 0.015, respectively) in cervical cancer patients. Moreover, patients with tumor tissue KIF2A high expression (mRNA and protein) displayed worse DFS (P = 0.010 and P = 0.046, respectively) and OS (P = 0.042 and P = 0.030, respectively) compared to patients with tumor tissue KIF2A low expression (mRNA and protein). Tumor tissue KIF2A expression could serve as a biomarker enhancing the disease surveillance and prognostication in cervical cancer management.

Association of kinesin family member 2A with increased disease risk, deteriorative clinical characteristics, and shorter survival profiles in acute myeloid leukemia.

This study aimed to explore the correlation of kinesin family member 2A (KIF2A) expression with disease risk, clinical characteristics, and prognosis of acute myeloid leukemia (AML), and investigate the effect of KIF2A knockdown on AML cell activities in vitro. Bone marrow samples were collected from 176 AML patients and 40 healthy donors, and KIF2A expression was measured by real-time quantitative polymerase chain reaction. Treatment response, event-free survival (EFS), and overall survival (OS) were assessed in AML patients. In vitro, KIF2A expression in AML cell lines and CD34+ cells (from healthy donors) was measured, and the effect of KIF2A knockdown on AML cell proliferation and apoptosis in HL-60 and KG-1 cells was detected. KIF2A expression was greater in AML patients compared to healthy donors, and receiver operating characteristic curve indicated that KIF2A expression predicted increased AML risk (area under curve: 0.793 (95%CI: 0.724-0.826)). In AML patients, KIF2A expression positively correlated with white blood cells, monosomal karyotype, and high risk stratification. Furthermore, no correlation of KIF2A expression with complete remission or hematopoietic stem cell transplantation was found. Kaplan-Meier curves showed that KIF2A expression was negatively correlated with EFS and OS. In vitro experiments showed that KIF2A was overexpressed in AML cell lines (KG-1, HL-60, ME-1, and HT-93) compared to CD34+ cells, moreover, cell proliferation was reduced but apoptosis was increased by KIF2A knockdown in HL-60 and KG-1 cells. In conclusion, KIF2A showed potential to be a biomarker and treatment target in AML.

Circular RNA circ_0010235 sponges miR-338-3p to play oncogenic role in proliferation, migration and invasion of non-small-cell lung cancer cells through modulating KIF2A

Background Circular RNA microarray analysis showed hsa_circ_0010235 (circ_0010235) was highly upregulated in non-small-cell lung cancer (NSCLC) patients; however, its role in carcinogenesis and development of NSCLC cells was unrevealed. Here, we intended to investigate role and mechanism of circ_0010235 in NSCLC proliferation, migration and invasion. Methods and results Expression of circ_0010235, microRNA (miR)-338-3p and kinesin family member 2A (KIF2A) was detected by quantitative real-time PCR, western blotting and immunohistochemistry (IHC). Cell progression was measured by cell-counting kit-8 assay, 5-ethynyl-2-deoxyuridine (EdU) assay, flow cytometry, transwell assay, western blotting, IHC and xenograft experiment. The relationship among circ_0010235, miR-338-3p and KIF2A was determined by dual-luciferase reporter assay, RNA immunoprecipitation and Pearson’s correlation analysis. Expression of circ_0010235 was increased in human NSCLC tissues and cells, accompanied with miR-338-3p downregulation and KIF2A upregulation. Essentially, circ_0010235 could sponge miR-338-3p via target binding, and miR-338-3p downstream targeted KIF2A. Functionally, exhaustion of circ_0010235 induced apoptosis rate of NSCLC cells and curbed cell viability, EdU incorporation, migration rate and invasion rate, accompanied with higher E-cadherin and lower N-cadherin expression. Additionally, re-expression of miR-338-3p prompted above similar effects in NSCLC cells in vitro. Contrarily, miR-338-3p blockage partially counteract the effects of circ_0010235 exhaustion; plus, restoration of KIF2A could attenuate miR-338-3p role, as well. Notably, interfering circ_0010235 delayed tumour growth of NSCLC cells by promoting miR-338-3p and E-cadherin expression, and depressing KIF2A, ki-67 and N-cadherin expression. Conclusions circ_0010235 could be a novel identified oncogenic circRNA in NSCLC, and targeting miR-338-3p/KIF2A axis was one regulatory mechanism underlying circ_0010235. KEY MESSAGE Circ_0010235 was an upregulated circRNA in NSCLC patients and cells. Interfering circ_0010235 restrained NSCLC cell proliferation and metastasis in vitro and in vivo. miR-338-3p per se suppressed NSCLC in vitro and its downregulation diminished the tumour-suppressive role of circ_0010235 blockage in NSCLC cells. miR-338-3p could downstream target KIF2A and be sponged by circ_0010235.

Identification of Kinesin Family Member 2A (KIF2A) as a Promising Therapeutic Target for Osteosarcoma.

Background Osteosarcoma is known as a type of common human bone malignancy, and more therapeutic targets are still required to combat this disease. In recent years, the involvement of KIF2A in cancer progression has been widely revealed; however, its potential effect on osteosarcoma development remains unknown. This study is to assess the KIF2A expression levels in human osteosarcoma tissues and explore its potential role in osteosarcoma development. Methods Immunohistochemical (IHC) assays were conducted to evaluate the expression levels of KIF2A in a total of 74 samples of osteosarcoma tissues and adjacent nontumor tissues. According to the staining intensity in tumor tissues, patients were divided into highly expressed and low expression KIF2A groups. The possible links between the KIF2A expression and the clinical pathological features were explored and analyzed, and the effects of KIF2A on osteosarcoma cell proliferation, migration, and invasion were detected through colony formation assay, MTT assay, wound closure assay, and transwell assay, respectively. The effects of KIF2A on tumor growth and metastasis were detected by the use of animal models. Results KIF2A was highly expressed in human osteosarcoma tissues. Meanwhile, KIF2A was obviously correlated to the tumor size (P = 0.001∗) and clinical stage (P = 0.014∗) of osteosarcoma patients. Our results also revealed that the ablation of KIF2A dramatically blocked the proliferation, migration, and invasion capacity of osteosarcoma cells in vitro and blocked tumor growth and metastasis in mice. Conclusions We investigated the involvement of KIF2A in the development and metastasis of osteosarcoma and therefore thought KIF2A as a promising therapeutic target for osteosarcoma treatment.

Kinesin family member 2A high expression correlates with advanced tumor stages and worse prognosis in non-small cell lung cancer patients.

BackgroundThis present study was to explore the association of kinesin family member 2A (KIF2A) expression with clinicopathological features and survival profiles, and the effect of KIF2A on cell proliferation and chemosensitivity in non‐small cell lung cancer (NSCLC).MethodsTumor and paired adjacent specimens were collected from 380 patients with NSCLC underwent resection for immunohistochemistry assay of KIF2A expression. In vitro, the effect of KIF2A on cell proliferation, chemosensitivity to cisplatin/vinorelbine was detected via KIF2A plasmids transfection into NCI‐H1299 NSCLC cells.ResultsKinesin family member 2A expression was upregulated in tumor tissues compared with adjacent tissues, and tumor tissue KIF2A high expression was associated with higher pathological grade (P < .001), larger tumor size (P = .021), lymph node metastasis (P = .044), and increased tumor‐node‐metastasis stage (P = .001). As for survival profiles, disease‐free survival (P < .001) and overall survival (P < .001) were worse in patients with KIF2A high expression compared with those with KIF2A low expression. Multivariate Cox's regression exhibited that KIF2A high expression was an independent predictive factor for lower DFS (P < .001) and OS (P < .001). In vitro, KIF2A promoted proliferation and decreased chemosensitivity to cisplatin but not vinorelbine in NCI‐H1299 NSCLC cells.ConclusionsThe correlation of KIF2A expression with tumor features, survival, and its cellular function implies its potential as a prognostic biomarker and a treatment target in NSCLC.

Kinesin Family Member 18A (KIF18A) Contributes to the Proliferation, Migration, and Invasion of Lung Adenocarcinoma Cells In Vitro and In Vivo.

Objective To determine the expression levels of KIF18A in lung adenocarcinoma and its relationship with the clinicopathologic features of patients undergoing radical colectomy and explore the potential role in the progression of lung adenocarcinoma. Methods Immunohistochemical assays were performed to explore the expression levels of KIF18A in 82 samples of lung adenocarcinoma and corresponding normal tissues. According to the levels of KIF18A expression in lung adenocarcinoma tissue samples, patients were classified into the KIF18A high expression group and low expression group. Clinical data related to the perioperative clinical features (age, gender, smoking, tumor size, differentiation, clinical stage, and lymph node metastasis), the potential correlation between KIF18A expression levels, and clinical features were analyzed, and the effects of KIF18A on lung adenocarcinoma cell proliferation, migration, and invasion were measured by colony formation assay, MTT assay, wound healing assay, and transwell assays. The possible effects of KIF18A on tumor growth and metastasis were measured in mice through tumor growth and tumor metastasis assays in vivo. Results KIF18A in lung adenocarcinoma tissues. Further, KIF18A was significantly associated to clinical characteristic features including the tumor size (P = 0.033) and clinical stage (P = 0.041) of patients with lung adenocarcinoma. Our data also investigated that KIF18A depletion dramatically impairs the proliferation, migration, and invasion capacity of lung adenocarcinoma cells in vitro and inhibits tumor growth and metastasis in mice. Conclusions Our study reveals the involvement of KIF18A in the progression and metastasis of lung adenocarcinoma and provides a novel therapeutic target for the treatment of lung adenocarcinoma.

High kinesin family member 18A expression correlates with poor prognosis in primary lung adenocarcinoma.

BackgroundLung adenocarcinoma (LUAD) is the most prevalent pathological subtype of lung cancer. Kinesin family member 18A (KIF18A) plays an important role in tumorigenesis. Its roles in breast cancer, colorectal cancer, and other tumors have been demonstrated; however, studies of KIF18A in LUAD are limited. This study aimed to determine the role of KIF18A in LUAD progression and prognostic prediction.MethodsKIF18A expression was examined in LUAD cells and tissues by immunohistochemistry and Western blotting. Cell proliferation assay was performed to study the role of KIF18A in LUAD cells. Correlations between KIF18A expression and clinicopathological features were analyzed. The role of KIF18A in LUAD prognosis was evaluated using data from The Cancer Genome Atlas (TCGA).ResultsKIF18A expression was increased in tumor cells and tissues. Downregulation of KIF18A expression resulted in the suppression of cancer cell proliferation in in vitro assays, and was particularly related to poor tumor differentiation, big tumor size, lymph node metastasis, and more advanced tumor stage. In the TCGA dataset, high KIF18A messenger RNA expression was associated with poor disease‐free and overall survival in patients with LUAD. In addition, multivariate analysis indicated that KIF18A is an independent prognostic factor of disease‐free and overall survival in LUAD.ConclusionsCollectively, our results demonstrate that KIFl8A is highly expressed in LUAD. KIFl8A plays an important role in LUAD cell proliferation, but is a poor prognostic factor.

Overexpression of KIF18A promotes cell proliferation, inhibits apoptosis, and independently predicts unfavorable prognosis in lung adenocarcinoma.

Kinesin family member 18A (KIF18A), as a member of the kinesin superfamily, is significantly overexpressed and abnormally functions in various human cancers. But, its expression profiling in the lung adenocarcinoma (LUAD) remains unclear. In the present work, using the data derived from the Cancer Genome Atlas (TCGA), we assessed the expression pattern and prognostic value of KIF18A in LUAD. In addition, we analyzed the underlying mechanism of its gene dysregulation. Experimental and bioinformatic analysis results showed that KIF18A expression was dramatically increased in LUAD tissues compared with the normal counterparts. Moreover, the patients with high KIF18A expression had significantly poorer overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate analyses indicated that increased KIF18A expression was independently associated with unfavorable OS and RFS. In addition, by analyzing deep sequencing data from TCGA-LUAD, we found that KIF18A mutation was detected in 2.6% of LUAD cases, and increased KIF18A expression was associated with genetic amplification rather than DNA methylation. Moreover, gene co-expression network analysis revealed that a total of 339 KIF18A co-expressed genes were detected and enriched in several tumor-related pathways, especially cell cycle. Knockdown of KIF18A significantly inhibited cell proliferation in vitro and in vivo. Furthermore, silencing KIF18A induced LUAD cells apoptosis and arrested the cell cycle in the G2/M phase. KIF18A promotes cell proliferation, inhibits apoptosis, and is a valuable prognostic predictor and potential therapeutic target for the patients with LUAD. © 2019 IUBMB Life, 2019.

Regulation of KIF2A by Antitumor miR-451a Inhibits Cancer Cell Aggressiveness Features in Lung Squamous Cell Carcinoma.

In the human genome, miR-451a is encoded close to the miR-144 on chromosome region 17q11.2. Our previous study showed that both strands of pre-miR-144 acted as antitumor miRNAs and were involved in lung squamous cell carcinoma (LUSQ) pathogenesis. Here, we aimed to investigate the functional significance of miR-451a and to identify its targeting of oncogenic genes in LUSQ cells. Downregulation of miR-451a was confirmed in LUSQ clinical specimens, and low expression of miR-451a was significantly associated with poor prognosis of LUSQ patients (overall survival: p = 0.035, disease-free survival: p = 0.029). Additionally, we showed that ectopic expression of miR-451a significantly blocked cancer cell aggressiveness. In total, 15 putative oncogenic genes were shown to be regulated by miR-451a in LUSQ cells. Among these targets, high kinesin family member 2A (KIF2A) expression was significantly associated with poor prognosis (overall survival: p = 0.043, disease-free survival: p = 0.028). Multivariate analysis showed that KIF2A expression was an independent prognostic factor in patients with LUSQ (hazard ratio = 1.493, p = 0.034). Aberrant KIF2A expression promoted the malignant transformation of this disease. Analytic strategies based on antitumor miRNAs and their target oncogenes are effective tools for identification of novel molecular pathogenesis of LUSQ.

Kinesin family member-18A (KIF18A) is a predictive biomarker of poor benefit from endocrine therapy in early ER+ breast cancer.

Identification of effective and reliable biomarkers that could be used to predict the efficacy of endocrine therapy is of crucial importance to the management of oestrogen receptor positive (ER+) breast cancer (BC). KIF18A, a key regulator of cell cycle, is overexpressed in many human cancers, including BC. In this study, we investigated the role of KIF18A as a biomarker to predict the benefit from endocrine treatment in early ER + BC patients. KIF18A expression was assessed at the genomic level using the METABRIC dataset to explore its prognostic and predictive value in ER + BC patients (n = 1506). Predictive significance of KIF18A mRNA was validated using KM-Plot datasets (n = 2061). KIF18A protein expression was assessed using immunohistochemistry in a large annotated series of early-stage ER + BC (n = 1592) with long-term follow-up. High mRNA and protein expression of KIF18A were associated with short recurrence-free survival (RFS), distant-metastasis free survival (DMFS) and BC specific survival (all P < 0.05) in ER + BC in patients who received no adjuvant treatment or adjuvant endocrine therapy. In multivariate analysis, high KIF18A expression was an independent prognostic biomarker for poor RFS (P = 0.027) and DMFS (P = 0.028) in patients treated with adjuvant endocrine therapy. KIF18A appears to be a candidate biomarker of a subgroup of ER + BC characterised by poor clinical outcome. High KIF18A expression has prognostic significance to predict poor benefit from endocrine treatment for patients with ER + BC. Therefore, measurement of KIF18A on ER + BC patients prior to treatment could guide clinician decision on benefit from endocrine therapy.

High KIF2A expression promotes proliferation, migration and predicts poor prognosis in lung adenocarcinoma

The Kinesin family member 2a (KIF2A), that belongs to the Kinesin-13 microtubule depolymerases, plays an important role in cancer cell proliferation, migration and apoptosis in various types of cancer such as gastric cancer, breast cancer, and squamous cell carcinoma of the oral tongue, but, its role and mechanism in lung adenocarcinoma (LUAD) is largely unknown. The present study reported that KIF2A was overexpressed in LUAD tissues as compared with adjacent normal tissues. KIF2A was closely correlated with TNM stage and lymph node metastasis (P < 0.01), whereas, no similar relationships between KIF2A and age, gender, smoking and differentiation. Multivariate analysis indicated that hyperexpression of KIF2A in LUAD was an independent risk factor for worse overall survival in LUAD patients (HR: 3.135, 95%CI: 1.331–7.112, p < 0.05). In vitro, KIF2A knockdown markedly reduced LUAD cell A549 migration and could regulate epithelial-mesenchymal transition. Furthermore, silencing KIF2A inhibited cell proliferation and induced apoptosis in lung adenocarcinoma(LUAD) cells. In conclusion, KIF2A may serve as a valuable prognostic indicator and promising therapeutic target of LUAD.

High KIF2A expression predicts unfavorable prognosis in diffuse large B cell lymphoma

Kinesin family member 2A (KIF2A), a conserved motor protein, plays a critical role in the pathogenesis and prognosis of several malignant tumors. The aim of the present study was to investigate KIF2A expression in diffuse large B cell lymphoma (DLBCL), evaluate the association between KIF2A expression and the clinical parameters of the disease, and determine its prognostic value. KIF2A expression was evaluated in 134 DLBCL and 57 reactive hyperplasia samples using immunohistochemistry on a tissue microarray. The correlations between KIF2A expression with clinical parameters and prognosis were estimated using univariate and multivariate analyses. The expression of KIF2A was significantly higher in DLBCL tissue samples compared with those from subjects with reactive hyperplasia (P=0.002). Furthermore, increased expression of KIF2A protein in DLBCL was related to Ann Arbor stage (P=0.027) and international prognostic index (IPI) score (P=0.01). The survival analysis showed that KIF2A expression (P=0.016), serum LDH level (P=0.049), and IPI score (P<0.001) were independent prognostic markers for DLBCL. Our findings also confirmed that downregulating KIF2A expression decreased tumor cell viability, accompanied by downregulation of pAKT levels. Taken together, these data provide the first evidence that increased KIF2A expression predicts poor prognosis in patients with DLBCL, and a rationale for treatment of DLBCL by targeting KIF2A.

Clinicopathological relevance of kinesin family member 18A expression in invasive breast cancer.

Recently, kinesin motor proteins have been focused on as targets for cancer therapy. Kinesins are microtubule-based motor proteins that mediate diverse functions within the cell, including the transport of vesicles, organelles, chromosomes and protein complexes, as well as the movement of microtubules. In the current study, the expression of kinesin family member 18A (KIF18A), a member of kinesin superfamily, was investigated in breast cancer using immunohistochemistry, and its effect on breast cancer prognosis was examined. KIF18A expression level was significantly associated with lymph node metastasis (P=0.047). In patients with high levels of KIF18A expression, survival was significantly poorer compared to patients with low levels of KIF18A expression (disease-free survival, P=0.030). Multivariate analysis revealed that venous invasion (hazard ratio, 9.22; 95% confidence interval, 3.90-23.66; P<0.001) and KIF18A expression (hazard ratio, 3.20; 95% confidence interval, 1.34-6.09; P=0.010) were independent predictive factors for lymph node metastasis. KIF18A may be a useful predictive marker for lymph node metastasis in breast cancer, which could facilitate curative adjuvant treatment.