TLN2 functions as a tumor suppressor in clear cell renal cell carcinoma via inactivation of the Wnt/β-catenin signaling pathway

Cai, Jingshuang; Huang, Zhiyu; Zhou, Jin; Wu, Wei; Ye, Yanle

doi:10.21037/tau-21-914

Cited by 8 publications

(7 citation statements)

References 32 publications

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“…Cai et al. found that low levels of TLN2 notably correlated with shorter survival rates and tumor aggressiveness in patients with ccRCC, and TLN2 strongly correlated with ccRCC proliferation, migration, and invasion via regulation of the Wnt/β‐catenin pathway 54 . However, the regulatory mechanism of their interaction in ccRCC has not been studied.…”

Section: Discussionmentioning

confidence: 99%

Exosome‐related lncRNA score: A value‐based individual treatment strategy for predicting the response to immunotherapy in clear cell renal cell carcinoma

Yang,

Zhang,

Zhan

et al. 2024

Cancer Medicine

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BackgroundExosomes play a crucial role in intercellular communication in clear cell renal cell carcinoma (ccRCC), while the long non‐coding RNAs (lncRNAs) are implicated in tumorigenesis and progression.AimsThe purpose of this study is to construction a exosomes‐related lncRNA score and a ceRNA network to predict the response to immunotherapy and potential targeted drug in ccRCC.MethodsData of ccRCC patients were obtained from the TCGA database. Pearson correlation analysis was used to identify eExosomes‐related lncRNAs (ERLRs) from Top10 exosomes‐related genes that have been screened. The entire cohort was randomly divided into a training cohort and a validation cohort in equal scale. LASSO regression and multivariate cox regression was used to construct the ERLRs‐based score. Differences in clinicopathological characteristics, immune microenvironment, immune checkpoints, and drug susceptibility between the high‐ and low‐risk groups were also investigated. Finally, the relevant ceRNA network was constructed by machine learning to analyze their potential targets in immunotherapy and drug use of ccRCC patients.ResultsA score consisting of 4ERLRs was identified, and patients with higher ERLRs‐based score tended to have a worse prognosis than those with lower ERLRs‐based score. ROC curves and multivariate Cox regression analysis demonstrated that the score could be considered as a risk factor for prognosis in both training and validation cohorts. Moreover, patients with high scores are predisposed to experience poor overall survival, a larger prevalence of advanced stage (III‐IV), a greater tumor mutational burden, a higher infiltration of immunosuppressive cells, and a greater likelihood of responding favorably to immunotherapy. The importance of EMX2OS was determined by mechanical learning, and the ceRNA network was constructed, and EMX2OS may be a potential therapeutic target, possibly exerting its function through the EMX2OS/hsa‐miR‐31‐5p/TLN2 axis.ConclusionsBased on machine learning, a novel ERLRs‐based score was constructed for predicting the survival of ccRCC patients. The ERLRs‐based score is a promising potential independent prognostic factor that is closely correlated with the immune microenvironment and clinicopathological characteristics. Meanwhile, we screened out key lncRNAEMX2OS and identified the EMX2OS/hsa‐miR‐31‐5p/TLN2 axis, which may provide new clues for the targeted therapy of ccRCC.

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Section: Discussionmentioning

confidence: 99%

Exosome‐related lncRNA score: A value‐based individual treatment strategy for predicting the response to immunotherapy in clear cell renal cell carcinoma

Yang,

Zhang,

Zhan

et al. 2024

Cancer Medicine

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“…Both talin1 and talin2 correlate with the malignancy potential of the human hepatocellular carcinoma MHCC-97 L cells [ 57 ]. Conversely, talin2 is downregulated in clear cell renal cell carcinoma (ccRCC) tissues and cells, and its overexpression in ccRCC cell lines inhibits cell growth and metastasis [ 58 ]. It remains to be discovered which factors influence the role of talin2 in tumors.…”

Section: Discussionmentioning

confidence: 99%

Talin2 and KANK2 functionally interact to regulate microtubule dynamics, paclitaxel sensitivity and cell migration in the MDA-MB-435S melanoma cell line

Lončarić,

Stojanović,

Rac-Justament

et al. 2023

Cell Mol Biol Lett

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Background Focal adhesions (FAs) are integrin-containing, multi-protein structures that link intracellular actin to the extracellular matrix and trigger multiple signaling pathways that control cell proliferation, differentiation, survival and motility. Microtubules (MTs) are stabilized in the vicinity of FAs through interaction with the components of the cortical microtubule stabilizing complex (CMSC). KANK (KN motif and ankyrin repeat domains) family proteins within the CMSC, KANK1 or KANK2, bind talin within FAs and thus mediate actin-MT crosstalk. We previously identified in MDA-MB-435S cells, which preferentially use integrin αVβ5 for adhesion, KANK2 as a key molecule enabling the actin-MT crosstalk. KANK2 knockdown also resulted in increased sensitivity to MT poisons, paclitaxel (PTX) and vincristine and reduced migration. Here, we aimed to analyze whether KANK1 has a similar role and to distinguish which talin isoform binds KANK2. Methods The cell model consisted of human melanoma cell line MDA-MB-435S and stably transfected clone with decreased expression of integrin αV (3αV). For transient knockdown of talin1, talin2, KANK1 or KANK2 we used gene-specific siRNAs transfection. Using previously standardized protocol we isolated integrin adhesion complexes. SDS-PAGE and Western blot was used for protein expression analysis. The immunofluorescence analysis and live cell imaging was done using confocal microscopy. Cell migration was analyzed with Transwell Cell Culture Inserts. Statistical analysis using GraphPad Software consisted of either one-way analysis of variance (ANOVA), unpaired Student’s t-test or two-way ANOVA analysis. Results We show that KANK1 is not a part of the CMSC associated with integrin αVβ5 FAs and its knockdown did not affect the velocity of MT growth or cell sensitivity to PTX. The talin2 knockdown mimicked KANK2 knockdown i.e. led to the perturbation of actin-MT crosstalk, which is indicated by the increased velocity of MT growth and increased sensitivity to PTX and also reduced migration. Conclusion We conclude that KANK2 functionally interacts with talin2 and that the mechanism of increased sensitivity to PTX involves changes in microtubule dynamics. These data elucidate a cell-type-specific role of talin2 and KANK2 isoforms and we propose that talin2 and KANK2 are therefore potential therapeutic targets for improved cancer therapy. Graphical Abstract

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“…In line with these findings, Xu et al (2022) demonstrated that the upregulation of SDHA resulted in a significant suppression of the Wnt/ β -catenin signal pathway by decreasing the β -catenin expression in ccRCC. Moreover, the activator of Wnt/ β -catenin signal pathway can attenuate the inhibition on the malignancy of ccRCC cells caused by TLN2 overexpression ( Cai et al, 2022 ). And SOX17 displayed the similar function as TLN2 ( Wang et al, 2021a ).…”

Section: Discussionmentioning

confidence: 99%

TTC13 expression and STAT3 activation may form a positive feedback loop to promote ccRCC progression

Xie,

Fang,

Chen

et al. 2023

PeerJ

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Background Renal cell carcinoma (RCC) originates from renal tubular epithelial cells and is mainly classified into three histological types, including clear cell renal cell carcinoma (ccRCC) which accounts for about 75% of all kidney cancers and is characterized by its strong invasiveness and poor prognosis. Hence, it is imperative to understand the mechanisms underlying the occurrence and progression of ccRCC to identify effective biomarkers for the early diagnosis and the prognosis prediction. Methods The mRNA level of TTC13 was quantified by RT-PCR, while the protein level was determined by western blot and immunohistochemistry (IHC) staining. Cell proliferation was measured by cck-8, and cell apoptosis was detected by flow cytometry. The binding of STAT3 to the promoter region of TTC13 was determined by the luciferase reporter assay and chip experiments. STAT3 nuclear translocation was assessed by immunofluorescence staining. Results We found that TTC13 was up-regulated in ccRCC, and TTC13 promoted cell proliferation as well as inhibited cell apoptosis and autophagy of ccRCC through wnt/β-catenin and IL6-JAK-STAT3 signaling pathways. Furthermore, TTC13 might play a role in the immune infiltration and immunotherapy of ccRCC. Mechanistically, STAT3 activated the transcription of TTC13 gene. Conclusions STAT3 directly regulated TTC13 expression through a positive feedback loop mechanism to promote ccRCC cell proliferation as well as reduce cell apoptosis and autophagy. These findings suggested new and effective therapeutic targets for more accurate and personalized treatment strategies.

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TLN2 functions as a tumor suppressor in clear cell renal cell carcinoma via inactivation of the Wnt/β-catenin signaling pathway

Cited by 8 publications

References 32 publications

Exosome‐related lncRNA score: A value‐based individual treatment strategy for predicting the response to immunotherapy in clear cell renal cell carcinoma

Exosome‐related lncRNA score: A value‐based individual treatment strategy for predicting the response to immunotherapy in clear cell renal cell carcinoma

Talin2 and KANK2 functionally interact to regulate microtubule dynamics, paclitaxel sensitivity and cell migration in the MDA-MB-435S melanoma cell line

TTC13 expression and STAT3 activation may form a positive feedback loop to promote ccRCC progression

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