miR-638 promotes melanoma metastasis and protects melanoma cells from apoptosis and autophagy

Bhattacharya, Animesh; Schmitz, Ulf; Raatz, Yvonne; Schönherr, Madeleine; Kottek, Tina; Schauer, Marianne; Franz, Sandra; Saalbach, Anja; Anderegg, Ulf; Wolkenhauer, Olaf; Schadendorf, Dirk; Simon, Jan C.; Magin, Thomas M.; Vera, Julio; Kunz, Manfred

doi:10.18632/oncotarget.3070

Cited by 75 publications

(61 citation statements)

References 39 publications

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“…In this study, miR-638 was not found to affect GC cells apoptosis (result not shown). However, in other studies, miR-638 was found to protect melanoma cells from apoptosis and autophagy [25], and promote starvation-or rapamycin-induced autophagy in ESCC and breast cells (KYSE450 and MCF-7) [26]. SOX2, a member of SRY-related HMG-box transcription factors families, is a well-established regulator of cell differentiation and development [27,28].…”

Section: Discussionmentioning

confidence: 97%

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miR-488 acts as a tumor suppressor gene in gastric cancer

Zhao

et al. 2016

Tumor Biol.

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Gastric cancer is one of the major causes of cancer mortality. Several microRNAs play a role in the tumor growth and invasion. However, the underlying molecular mechanism remains poorly understood. We detected the miR-638 expression levels in tumor samples and adjacent noncancerous tissues from 68 patients with gastric cancer as well as in the gastric cancer cell line SGC-7901 and SC-M1. The cell cycle was analyzed by flow cytometry, cell proliferation was observed by CCK-8 assay and cell invasion was detected using Transwell assay. MiR-638 was down-regulated in human GC tissues and its expression level was negatively correlated to TNM stage and lymph metastasis. In the cell lines, aberrant expression of miR-638 was related to the cell proliferation, cell cycle and invasion. We also found that SOX2 had a negative correlation with miR-638 in GC tissues, and miR-638 overexpression could decrease SOX2 expression level by directly binding the 3'-UTR of SOX2. in vitro, downregulating SOX2 by siRNA could counteract the effect of miR-638 inhibitor on GC cells proliferation and invasion. Our results demonstrate that miR-638 may play a pivotal role in the growth and invasion of GC.

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Section: Discussionmentioning

confidence: 97%

“…But Bhattacharya A et al reported that miR-638 could protect melanoma cells from apoptosis and autophagy and promote melanoma metastasis [25]. Ren Y et al also found miR-638 acting as an oncogene in esophageal squamous cell carcinoma (ESCC) and breast cancer [26], paradoxical with Tan X et al [19].…”

Section: Discussionmentioning

confidence: 99%

miR-488 acts as a tumor suppressor gene in gastric cancer

Zhao

et al. 2016

Tumor Biol.

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“…Our data, in addition to other studies (Jin et al , ), indicate that p62 interacts with ubiquitinated caspase‐8 and facilitates its aggregation and full activation. Since both p62 and TP53INP2 are involved in differentiation (Linares et al , ; McManus & Roux, ; Li et al , ; Sugiyama et al , ), apoptosis (Jin et al , ; Moscat & Diaz‐Meco, ; Bhattacharya et al , ), nuclear hormone receptor signaling (Baumgartner et al , ; Duran et al , ), diabetes (Sala et al , ; Kruse et al , ; Long et al , ), and autophagy (Pankiv et al , ; Moscat & Diaz‐Meco, ; Nowak et al , ; Mauvezin et al , ; Sancho et al , ), further studies are needed to unravel how they interplay/overlap in these pathways. Along the same line, TRAF6 has been implicated in multiple signaling pathways, such as autophagy, development, and immunity (Linares et al , ; Walsh et al , ).…”

Section: Discussionmentioning

confidence: 99%

Regulation of death receptor signaling by the autophagy protein TP 53 INP 2

et al. 2019

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TP53INP2 positively regulates autophagy by binding to Atg8 proteins. Here, we uncover a novel role of TP53INP2 in deathreceptor signaling. TP53INP2 sensitizes cells to apoptosis induced by death receptor ligands. In keeping with this, TP53INP2 deficiency in cultured cells or mouse livers protects against death receptor-induced apoptosis. TP53INP2 binds caspase-8 and the ubiquitin ligase TRAF6, thereby promoting the ubiquitination and activation of caspase-8 by TRAF6. We have defined a TRAF6-interacting motif (TIM) and a ubiquitin-interacting motif in TP53INP2, enabling it to function as a scaffold bridging already ubiquitinated caspase-8 to TRAF6 for further polyubiquitination of caspase-8. Mutations of key TIM residues in TP53INP2 abrogate its interaction with TRAF6 and caspase-8, and subsequently reduce levels of death receptor-induced apoptosis. A screen of cancer cell lines showed that those with higher protein levels of TP53INP2 are more prone to TRAIL-induced apoptosis, making TP53INP2 a potential predictive marker of cancer cell responsiveness to TRAIL treatment. These findings uncover a novel mechanism for the regulation of caspase-8 ubiquitination and reveal TP53INP2 as an important regulator of the death receptor pathway.

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“…miR-638 induces its pro-tumorigenic and metastatic effects, protecting melanoma cells from apoptosis and autophagy. Knockdown of miR-638 increases TP53INP2 expression and stimulates expression of p53 and p53 downstream target genes, inducing significant apoptosis and autophagy [29].…”

Section: Mirnas Acting As Oncogenesmentioning

confidence: 99%

miRNAs as Key Players in the Management of Cutaneous Melanoma

Lorusso

Summa

Pinto

et al. 2020

Cells

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The number of treatment options for melanoma patients has grown in the past few years, leading to considerable improvements in both overall and progression-free survival. Targeted therapies and immune checkpoint inhibitors have opened a new era in the management of melanoma patients. Despite the clinical advances, further research efforts are needed to identify other "druggable" targets and new biomarkers to improve the stratification of melanoma patients who could really benefit from targeted and immunotherapies. To this end, many studies have focused on the role of microRNAs (miRNAs) that are small non-coding RNAs (18-25 nucleotides in length), which post-transcriptionally regulate the expression of their targets. In cancer, they can behave either as oncogenes or oncosuppressive genes and play a central role in many intracellular pathways involved in proliferation and invasion. Given their modulating activity on the transcriptional landscape, their biological role is under investigation to study resistance mechanisms. They are able to mediate the communication between tumor cells and their microenvironment and regulate tumor immunity through direct regulation of the genes involved in immune activation or suppression. To date, a very promising miRNA-based strategy is to use them as prognosis and diagnosis biomarkers both as cell-free miRNAs and extracellular-vesicle miRNAs. However, miRNAs have a complex role since they target different genes in different cellular conditions. Thus, the ultimate aim of studies has been to recapitulate their role in melanoma in biological networks that account for miRNA/gene expression and mutational state. In this review, we will provide an overview of current scientific knowledge regarding the oncogenic or oncosuppressive role of miRNAs in melanoma and their use as biomarkers, with respect to approved therapies for melanoma treatment.

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miR-638 promotes melanoma metastasis and protects melanoma cells from apoptosis and autophagy

Cited by 75 publications

References 39 publications

miR-488 acts as a tumor suppressor gene in gastric cancer

miR-488 acts as a tumor suppressor gene in gastric cancer

Regulation of death receptor signaling by the autophagy protein TP 53 INP 2

miRNAs as Key Players in the Management of Cutaneous Melanoma

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