TMED3/RPS15A Axis promotes the development and progression of osteosarcoma

Xu, Wei; Li, Yifan; Ye, Xiaojian; Ji, Yunhan; Chen, Yu; Zhang, Xiangyang; Li, Zhikun

doi:10.1186/s12935-021-02340-w

Cited by 12 publications

(9 citation statements)

References 72 publications

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“…53 In-vitro studies have shown that the downregulation of RPS15A suppresses the cellular proliferation of osteosarcoma, lung cancer, breast cancer, acute myeloid leukemia and hepatocellular carcinoma. 54 Overexpression of RPS15A promotes proliferation, metastasis and EMT via activation of the AKT signaling pathway in gastric cancer cells. 55 Despite the important component of the ribosomal complex, the role of RPS15A in the NED of PCa is not fully understood.…”

Section: Conflict Of Interest Statementmentioning

confidence: 99%

MicroRNA‐147b induces neuroendocrine differentiation of prostate cancer cells by targeting ribosomal protein RPS15A

et al. 2023

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Background Prostate cancer (PCa) is the leading cause of cancer related deaths in men, often androgen deprivation therapy (ADT) leads to the progression of androgen independent PCa (AIPC) which further leads to Neuroendocrine PCa (NEPC). Identifying the molecular mechanisms which navigate the neuroendocrine differentiation (NED) of PCa cells is clinically relevant. It has been suggested that the micro RNAs (miRNAs) play an important role in the regulation of intrinsic mechanisms relevant to tumor progression, resistance as a result leads to poor prognosis. miR‐147b has been transpiring as one of the deregulated miRNAs associated with the occurrence of multiple cancers. The present study has studied the role of miRNA‐147b in inducing NEPC. Methods To investigate the functional role of miR‐147b in NEPC, we have expressed miRNA mimics or inhibitors in PCa cells and monitored the progression of NEPC along with PCa cell proliferation and survival. The molecular mechanism miRNA‐147b follows was studied using western blot and reverse transcription polymerase chain analysis. miRNA target prediction using bioinformatics tools followed by target validation using luciferase reporter assays was performed. Results In the present study, we found that miR‐147b is highly expressed in AIPC cell lines in particular neuroendocrine cells NCI‐H660 and NE‐LNCaP derived from LNCaP. Mechanistic studies revealed that overexpression of miR‐147b or miRNA mimics induced NED in LNCaP cells in in‐vitro while its inhibitor reversed the NE features (increased NE markers and reduced prostate specific antigen) of PC3, NCI‐H660 and NE‐LNCaP cells. In addition, miR‐147b reduced the proliferation rate of LNCaP cells via elevated p27kip1 and lowered cyclin D1 for promoting differentiation. In reporter assays, we have identified ribosomal protein S15A (RPS15A) is a direct target of miRNA‐147b and RPS15A expression was negatively regulated by miR‐147b in PCa cells. Furthermore, we also report that RPS15A is downregulated in NEPC cells and its expression is inversely correlated with NE markers. Conclusion Targeting the miR‐147b ‐ RPS15A axis may overcome the progression of NEPC and serve as a novel therapeutic target to attenuate NED progression of PCa.

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Section: Conflict Of Interest Statementmentioning

confidence: 99%

MicroRNA‐147b induces neuroendocrine differentiation of prostate cancer cells by targeting ribosomal protein RPS15A

et al. 2023

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“…TMED3 plays a role in the selection and secretion of COP vesicles in the ER-GC network and modulates several signaling pathways. TMED3 expression is strongly upregulated in several cancer types (including osteosarcoma, breast cancer, chordoma, HCC and non-small cell lung cancer (NSCLC)) and correlates with poor prognosis in patients [54][55][56][57]121]. TMED3 function is required for WNT ligands normal intracellular localization, trafficking and secretion [122,123].…”

Section: Tmed Family Of P24 Proteinsmentioning

confidence: 99%

Golgi Complex: A Signaling Hub in Cancer

Spano

Colanzi

2022

Cells

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The Golgi Complex is the central hub in the endomembrane system and serves not only as a biosynthetic and processing center but also as a trafficking and sorting station for glycoproteins and lipids. In addition, it is an active signaling hub involved in the regulation of multiple cellular processes, including cell polarity, motility, growth, autophagy, apoptosis, inflammation, DNA repair and stress responses. As such, the dysregulation of the Golgi Complex-centered signaling cascades contributes to the onset of several pathological conditions, including cancer. This review summarizes the current knowledge on the signaling pathways regulated by the Golgi Complex and implicated in promoting cancer hallmarks and tumor progression.

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“…The oncogenic role of TMED3 was also verified in breast cancer development through clinicopathological data and in vitro and vivo experiments [ 10 ]. TMED3 knockdown also inhibited osteosarcoma cell proliferation and tumor growth by inhibiting RPS15A [ 11 ]. However, TMED3 was also reported as a metastatic suppressor and knocking down TMED3 could promote metastatic growth in human colon cancer [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Depleting TMED3 alleviates the development of endometrial carcinoma

Zhang

2022

Cancer Cell Int

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Background As one of gynecologic tumors, endometrial carcinoma (EC) has been characterized by high incidence rate, but its molecular pathogenesis has remained unclear. TMED3 is a membrane protein and has been indicated to implicate several tumor-related diseases. In the current study, we aimed to explore the physiological function of TMED3 in EC progression. Methods Through bioinformatic analysis using The Cancer Genome Atlas database and immunohistochemistry assay on tissue microarray, we examined whether TMED3 was upregulated in EC tissues. After constructing TMED3-knockdown cell models via lentiviral transfection, qPCR and western blot were employed to determine the expression levels of TMED3 mRNA and protein. Then, Celigo cell counting assay, CCK8 assay, flow cytometry, wound-healing assay and Transwell assay were used to detect cell proliferation, cell cycle, cell apoptosis and cell migration, respectively. Results As a result, it was found that TMED3 was upregulated in EC cells, which was also verified in clinical samples. We then found that downregulation of TMED3 considerably restrained cell cycle, cell growth and migration but promoted apoptosis of EC cells. The following in-vivo experiments also verified that tumor growth was inhibited after TMED3 knockdown. The exploration in molecular mechanisms showed that TMED3 deletion may weaken cellular viability through upregulating pro-apoptotic proteins and targeting PI3K/AKT signaling pathways. Conclusions This study suggested that knocking down TMED3 affected the malignant phenotype of EC cells and thus limited tumor progression, which provided insights to the development of targeted drugs for EC treatment.

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TMED3/RPS15A Axis promotes the development and progression of osteosarcoma

Cited by 12 publications

References 72 publications

MicroRNA‐147b induces neuroendocrine differentiation of prostate cancer cells by targeting ribosomal protein RPS15A

MicroRNA‐147b induces neuroendocrine differentiation of prostate cancer cells by targeting ribosomal protein RPS15A

Golgi Complex: A Signaling Hub in Cancer

Depleting TMED3 alleviates the development of endometrial carcinoma

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