PVALB diminishes [Ca2+] and alters mitochondrial features in follicular thyroid carcinoma cells through AKT/GSK3β pathway

Mendes, Thais Biude; Nozima, Bruno Heidi Nakano; Budu, Alexandre; Souza, Rodrigo Barbosa de; Catroxo, Márcia Helena Braga; Delcelo, Rosana; Gazarini, Marcos L.; Cerutti, Janete M.

doi:10.1530/erc-16-0181

Cited by 9 publications

(6 citation statements)

References 36 publications

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“…In our study, the expression of PVALB was slightly higher in cases with suboptimal surgical resection. In contrast, PVALB expression has been reported to be higher in benign vs malignant thyroid lesions and in normal glial cells vs glioma [36,37].…”

Section: Discussionmentioning

confidence: 91%

Genes associated with bowel metastases in ovarian cancer

Mariani

Wang

Oberg

et al. 2019

Gynecologic Oncology

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We identified 21 genes overexpressed in ovarian cancer (OC) bowel metastases compared to primary tumors. • High expression of these genes in primary OCs is associated with a need of complex bowel surgery and poor prognosis.• These genes may help identify potential therapeutic targets of malignant bowel obstruction in OC. a b s t r a c tObjective. This study is designed to identify genes and pathways that could promote metastasis to the bowel in high-grade serous ovarian cancer (OC) and evaluate their associations with clinical outcomes.Methods. We performed RNA sequencing of OC primary tumors (PTs) and their corresponding bowel metastases (n = 21 discovery set; n = 18 replication set). Differentially expressed genes (DEGs) were those expressed at least 2-fold higher in bowel metastases (BMets) than PTs in at least 30% of patients (P b .05) with no increased expression in paired benign bowel tissue and were validated with quantitative reverse transcription PCR. Using an independent OC cohort (n = 333), associations between DEGs in PTs and surgical and clinical outcomes were performed. Immunohistochemistry and mouse xenograft studies were performed to confirm the role of LRRC15 in promoting metastasis.Results. Among 27 DEGs in the discovery set, 21 were confirmed in the replication set: SFRP2, Col11A1, LRRC15, ADAM12, ADAMTS12, MFAP5, LUM, PLPP4, FAP, POSTN, GRP, MMP11, MMP13, C1QTNF3, EPYC, DIO2, KCNA1, NETO1, NTM, MYH13, and PVALB. Higher expression of more than half of the genes in the PT was associated with an increased requirement for bowel resection at primary surgery and an inability to achieve complete cytoreduction. Increased expression of LRRC15 in BMets was confirmed by immunohistochemistry and knockdown of LRRC15 significantly inhibited tumor progression in mice.Conclusions. We identified 21 genes that are overexpressed in bowel metastases among patients with OC. Our findings will help select potential molecular targets for the prevention and treatment of malignant bowel obstruction in OC. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).

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Section: Discussionmentioning

confidence: 91%

Genes associated with bowel metastases in ovarian cancer

Mariani

Wang

Oberg

et al. 2019

Gynecologic Oncology

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“…PCCL3 cells with ectopic expression of FAM129A and control (empty vector) were fixed and stained as previously described (Mendes et al 2016). Cells were fixed in Karnovisky buffer (4% paraformaldehyde and 2% glutaraldehyde in 0.05 M sodium cacodylate buffer, pH 7.2) (Sigma-Aldrich).…”

Section: Monitoring Autophagosomes Formation By Transmission Electronmentioning

confidence: 99%

FAM129A regulates autophagy in thyroid carcinomas in an oncogene-dependent manner

Nozima

Mendes

Pereira

et al. 2019

Endocrine-Related Cancer

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We previously proposed that high expression of FAM129A can be used as a thyroid carcinoma biomarker in preoperative diagnostic exams of thyroid nodules. Here, we identify that FAM129A expression is increased under nutrient and growth factor depletion in a normal thyroid cell line (PCCL3), overlapping with increased expression of autophagyrelated protein and inhibition of AKT/mTOR/p70S6K. Supplementation of insulin, TSH and serum to the medium was able to reduce the expression of both FAM129A and autophagyrelated protein and reestablish the AKT/mTOR/p70S6K axis. To determine the direct role of FAM129A on autophagy, FAM129A was transfected into PCCL3 cells. Its overexpression induced autophagic vesicles formation, evidenced by transmission electron microscopy. Co-expression of FAM129A and mCherry-EGFP-LC3B in PCCL3 showed an increased yellow puncta formation, suggesting that FAM129Ainduces autophagy. To further confirm its role on autophagy, we knockdown FAM129A in two thyroid carcinoma cell lines (TPC1 and FTC-236). Unexpectedly, FAM129A silencing increased autophagic flux, suggesting that FAM129A inhibits autophagy in these models. We next co-transfected PCCL3 cells with FAM129A and RET/PTC1 and tested autophagy in this context. Co-expression of FAM129A and RET/PTC1 oncogene in PCCL3 cells, inhibited RET/PTC1-induced autophagy. Together, our data suggest that, in normal cells FAM129A induces autophagy in order to maintain cell homeostasis and provide substrates under starvation conditions. Instead, in cancer cells, decreased autophagy may help the cells to overcome cell death. FAM129A regulates autophagy in a cell-and/or context-dependent manner. Our data reinforce the concept that autophagy can be used as a strategy for cancer treatment.

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“…The TDRD12 and LIN28A together with TDRKH which also was upregulated in PTM/PM but downregulated in TM/PTM were enriched into 1 MF, GO:0050731∼positive regulation of peptidyl-tyrosine phosphorylation. Another one, PVALB, went on being upregulated at subsequent process, indicating its importance during the cancerization (Mendes et al, 2016;Zhong et al, 2018). The results demonstrated that those DEGs might have different physiological significance in the transitions from the PM to the PTM and from the PTM to the TM in biogenesis of a secondary tumor.…”

Section: Discussionmentioning

confidence: 88%

RNA binding proteins involved in regulation of protein synthesis to initiate biogenesis of secondary tumor in hepatocellular carcinoma in mice

Tang

et al. 2020

PeerJ

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Background The tumor microenvironment (TM) in close contact with cancer cells is highly related to tumor growth and cancer metastasis. This study is to explore the biogenesis mechanism of a secondary hepatocellular carcinoma (HCC) based on the function of RNA binding proteins (RBPs)-encoding genes in the physiological microenvironment (PM). Methods The healthy and HCC mice were used to isolate the PM, pre-tumor microenvironment (PTM), and TM. The samples were analyzed using the technology of RNA-seq and bioinformatics. The differentially expressed RBPs-encoding genes (DERs) and differentially expressed DERs-associated genes (DEDs) were screened to undergo GO and KEGG analysis. Results 18 DERs and DEDs were identified in the PTM vs. PM, 87 in the TM vs. PTM, and 87 in the TM vs. PM. Those DERs and DEDs participated in the regulation of gene expression at the levels of chromatin conformation, gene activation and silencing, splicing and degradation of mRNA, biogenesis of piRNA and miRNA, ribosome assemble, and translation of proteins. Conclusion The genes encoding RBPs and the relevant genes are involved in the transformation from PM to PTM, then constructing the TM by regulating protein synthesis. This regulation included whole process of biological genetic information transmission from chromatin conformation to gene activation and silencing to mRNA splicing to ribosome assemble to translation of proteins and degradation of mRNA. The abnormality of those functions in the organic microenvironments promoted the metastasis of HCC and initiated the biogenesis of a secondary HCC in a PM when the PM encountered the invasion of cancer cells.

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PVALB diminishes [Ca2+] and alters mitochondrial features in follicular thyroid carcinoma cells through AKT/GSK3β pathway

Cited by 9 publications

References 36 publications

Genes associated with bowel metastases in ovarian cancer

Genes associated with bowel metastases in ovarian cancer

FAM129A regulates autophagy in thyroid carcinomas in an oncogene-dependent manner

RNA binding proteins involved in regulation of protein synthesis to initiate biogenesis of secondary tumor in hepatocellular carcinoma in mice

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