Upregulation of the Kank1 gene inhibits human lung cancer progression in�vitro and in�vivo

Gu, Yingchun; Zhang, Min

doi:10.3892/or.2018.6526

Cited by 11 publications

(16 citation statements)

References 15 publications

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“…A series of studies had shown that KANK1 exerted an anti-cancer role in various tumors. For instance, increased KANK1 expression curbed the progression of gastric cancer [23] and lung cancer [28]. Moreover, KANK1 enhancement repressed cell cycle and accelerated cell apoptosis in brain glioma [49].…”

Section: Discussionmentioning

confidence: 99%

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Long non-coding RNA CASC2 enhances cisplatin sensitivity in oral squamous cell cancer cells by the miR-31-5p/KANK1 axis

Wang

Jia

Zhou

2021

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Oral squamous cell cancer (OSCC) is a primary malignant tumor of the head and neck. Long non-coding RNA cancer susceptibility candidate 2 (CASC2) is related to the chemoresistance of diverse tumors. At present, the resistance of OSCC to first-line chemotherapy drug cisplatin (DDP) is still a giant problem. Herein, we investigated the role and mechanism of CASC2 in OSCC resistance to DDP. Expression levels of CASC2, miR-31-5p, and KANK1 in OSCC tissues and cells were determined by qRT-PCR. The half-maximal inhibitory concentration (IC50) value of DDP-resistant OSCC cells and apoptosis of DDP-resistant OSCC cells were determined via CCK-8 or flow cytometry assays. The relationship between CASC2 or KANK1 and miR-31-5p was verified with a dual-luciferase reporter or RIP assays. The role o f CASC2 in vivo was confirmed by xenograft experiments. We observed that CASC2A and KANK1 were downregulated while miR-31-5p was upregulated in DDP-resistant OSCC tissues and cells (p < 0.05). CASC2 overexpression enhanced cell DDP sensitivity and accelerated cell apoptosis in DDP-resistant OSCC cells in vivo and in vitro (p < 0.05). Notably, KANK1 acted as a target for miR-31-5p. Also, CASC2 modulated KANK1 expression via sponging miR-31-5p in DDP-resistant OSCC cells (p < 0.05). Both CASC2 and KANK1 introduction-mediated impacts on the DDP sensitivity and apoptosis of DDP-resistant OSCC cells were restored by miR-31-5p elevation (p < 0.05). To conclude, CASC2 boosted the DDP sensitivity and apoptosis of DDP-resistant OSCC cells by upregulating KANK1 via sponging miR-31-5p, and CASC2 might be a potential target for DDP-resistant OSCC treatment.

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Section: Discussionmentioning

confidence: 99%

“…Also, KANK1 depletion promoted the amplification of the centrosomal [27]. Moreover, it was proved as a suppressor in various tumors [28][29][30]. For instance, KANK1 impeded the progression of human malignant peripheral nerve sheath tumors via promoting cell apoptosis [29].…”

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confidence: 99%

Long non-coding RNA CASC2 enhances cisplatin sensitivity in oral squamous cell cancer cells by the miR-31-5p/KANK1 axis

Wang

Jia

Zhou

2021

neo

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“…However, translocation of Bax and Bcl-2 may lead to changes in mitochondrial membrane proteins resulting in the release of cytochrome C, activating the Caspase family and eventually leading to apoptosis [36,37]. Recently, it has been reported that the up-regulation of the KANK1 gene can inhibit the development of lung cancer both in vivo and in vitro, and its mechanism is closely related to cell apoptosis and tumour invasion and metastasis [38].…”

Section: Discussionmentioning

confidence: 99%

KANK1 regulates paclitaxel resistance in lung adenocarcinoma A549 cells

Shen

Zhong

et al. 2020

Artificial Cells, Nanomedicine, and Biotechnology

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Paclitaxel (PTX), a tubulin-binding agent, is widely used and has shown good efficacy in the initial period of treatment for non-small cell lung cancer (NSCLC). However, the relatively rapid acquisition of resistance to PTX treatments that is observed in virtually all cases significantly limits its utility and remains a substantial challenge to the clinical management of NSCLC. The aim of this study was to identify candidate genes and mechanisms that might mediate acquired paclitaxel resistance. In this work, we established paclitaxel-resistant cells (A549-T) from parental cell lines by step-dose selection in vitro. Using methylation chip analysis and transcriptome sequencing, 43,426 differentially methylated genes and 2,870 differentially expressed genes are identified. Six genes (KANK1, ALDH3A1, GALNT14, PIK3R3, LRG1, WEE2), which may be related to paclitaxel resistance in lung adenocarcinoma, were identified. Among these genes, KANK1 exhibited significant differences in methylation and expression between cell lines. Since KANK1 plays an important role in the development of renal cancer and gastric cancer, we hypothesised that it may also play a role in acquired resistance in lung adenocarcinoma. Transient transfection of SiKANK1 significantly reduced the expression of KANK1, reducing apoptosis, increasing cell migration, and enhancing the tolerance of A549 cells to paclitaxel. KANK1 acts as a tumour suppressor gene, mediating the resistance of lung adenocarcinoma A549 to paclitaxel. The reduction of KANK1 expression can increase the paclitaxel resistance of non-small cell lung cancer and increase the difficulty of clinical treatment.

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“…To determine the protein levels of CXXC5, KANK1, EMT proteins (Vimentin and E-cadherin) and signaling proteins (β-catenin and Axin2), Western blotting was conducted followed the description of a previous study. 34 It is worth mentioning that the compositions of cell lysis buffer we used in the present study were radioimmunoprecipitation assay buffer (Thermo Fisher Scientific, Waltham, USA) and 1% phenylmethanesulfonyl fluoride (Seebio, Shanghai, China). Besides, the primary antibodies included anti-GAPDH (normalization protein), anti-CXXC5, anti-KANK1, anti-Vimentin, anti-E-cadherin, anti-β-catenin and anti-Axin2 (Cell Signaling Technology, Danvers, USA) with a dilution of 1:500.…”

Section: Western Blottingmentioning

confidence: 99%

<p>The KN Motif and Ankyrin Repeat Domains 1/CXXC Finger Protein 5 Axis Regulates Epithelial-Mesenchymal Transformation, Metastasis and Apoptosis of Gastric Cancer via Wnt Signaling</p>

Chen

Wang

et al. 2020

OTT

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Background: Emerging research indicates that CXXC finger protein 5 (CXXC5) is involved in the development of various cancers. Besides, KN motif and ankyrin repeat domains 1 (KANK1) was proved as a tumor suppressor in multiple cancers. Our study aimed to illustrate the functional role and mechanism of CXXC5 and KANK1 in gastric cancer (GC) pathogenesis. Methods: The tissues of 55 GC patients and six GC cell lines were used to investigate CXXC5 and KANK1 expression using RT-qPCR. Western blot assay was conducted to measure the protein levels of CXXC5, KANK1, epithelial-mesenchymal transformation (EMT) proteins (Vimentin, E-cadherin) and Wnt signaling proteins (β-catenin, Axin2). The correlation between KANK1 and CXXC5 was estimated by Pearson's correlation analysis. The results of Transwell assays showed the migration and invasion abilities of GC cells, while the apoptosis rate was detected by flow cytometry. Results: The expressions of CXXC5 and KANK1 were both decreased in GC tissues and cells, compared with the normal ones (P < 0.01). Overexpressing CXXC5 significantly induced apoptosis (P < 0.05) and inhibited EMT, migration (P < 0.05) and invasion (P < 0.01) in GC cells. Wnt/β-catenin/Axin2 signaling was suppressed by CXXC5 overexpression, and activating Wnt/β-catenin/Axin2 signaling reversed the effects of CXXC5. The expression of KANK1 was found to be positively correlated with CXXC5 (r 2 = 0.4024). KANK1 presented similar effects with CXXC5 on GC cells; however, silencing CXXC5 or activating Wnt/β-catenin/Axin2 signaling antagonized the effects of KANK1 overexpression on EMT and apoptosis in GC (P < 0.05). Conclusion: Our study suggested that CXXC5 was downregulated in GC and participated in EMT and apoptosis regulations via the Wnt/β-catenin/Axin2 pathway. Besides, the decreased expression of CXXC5 in GC was caused by KANK1 dysregulation.

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Upregulation of the Kank1 gene inhibits human lung cancer progression in�vitro and in�vivo

Cited by 11 publications

References 15 publications

Long non-coding RNA CASC2 enhances cisplatin sensitivity in oral squamous cell cancer cells by the miR-31-5p/KANK1 axis

Long non-coding RNA CASC2 enhances cisplatin sensitivity in oral squamous cell cancer cells by the miR-31-5p/KANK1 axis

KANK1 regulates paclitaxel resistance in lung adenocarcinoma A549 cells

<p>The KN Motif and Ankyrin Repeat Domains 1/CXXC Finger Protein 5 Axis Regulates Epithelial-Mesenchymal Transformation, Metastasis and Apoptosis of Gastric Cancer via Wnt Signaling</p>

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