LETM1 is a potential biomarker that predicts poor prognosis in gastric adenocarcinoma

Li, Haoyue; Piao, Lihua; Xu, Dongmei; Xuan, Yanhua

doi:10.1016/j.yexmp.2019.104333

Cited by 15 publications

(11 citation statements)

References 39 publications

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“…Many stem cell markers, such as CD44 and CD133, have critical roles in the formation and development of tumours 33,34 . Recent reports suggest that LETM1 is associated with cancer stem cell–like properties 35 . Herein, we found that LETM1 silencing resulted in down‐regulation of the CSC‐associated proteins CD44 and CD133 and decreased sphere‐forming ability.…”

Section: Discussionmentioning

confidence: 67%

Suppression of LETM1 inhibits the proliferation and stemness of colorectal cancer cells through reactive oxygen species–induced autophagy

Che

Yang

Liu

et al. 2020

J Cellular Molecular Medi

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Leucine zipper‐EF‐hand–containing transmembrane protein 1 (LETM1) is a mitochondrial inner membrane protein that is highly expressed in various cancers. Although LETM1 is known to be associated with poor prognosis in colorectal cancer (CRC), its roles in autophagic cell death in CRC have not been explored. In this study, we examined the mechanisms through which LETM1 mediates autophagy in CRC. Our results showed that LETM1 was highly expressed in CRC tissues and that down‐regulation of LETM1 inhibited cell proliferation and induced S‐phase arrest. LETM1 silencing also suppressed cancer stem cell–like properties and induced autophagy in CRC cells. Additionally, the autophagy inhibitor 3‐methyladenine reversed the inhibitory effects of LETM1 silencing on proliferation and stemness, whereas the autophagy activator rapamycin had the opposite effects. Mechanistically, suppression of LETM1 increased the levels of reactive oxygen species (ROS) and mitochondrial ROS by regulation of SOD2, which in turn activated AMP‐activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), initiated autophagy, and inhibited proliferation and stemness. Our findings suggest that silencing LETM1 induced autophagy in CRC cells by triggering ROS‐mediated AMPK/mTOR signalling, thus blocking CRC progression, which will enhance our understanding of the molecular mechanism of LETM1 in CRC.

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Section: Discussionmentioning

confidence: 67%

Suppression of LETM1 inhibits the proliferation and stemness of colorectal cancer cells through reactive oxygen species–induced autophagy

Che

Yang

Liu

et al. 2020

J Cellular Molecular Medi

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“…AMPK inhibition would lead to deregulation of the normal progression of the cell cycle. Accordingly, LETM1-KD reduced the expression of cancer stemness-related genes, increased AMPK activation, arrested cell cycle, lowered the number and size of tumor spheroids, and markedly inhibited cell proliferation (Che et al, 2020;Li et al, 2020;Piao et al, 2020).…”

Section: Letm1 In Cancermentioning

confidence: 98%

“…LETM1-mediated regulation of mitochondrial biogenesis, metabolism, and cell survival signaling has provided impetus to investigate LETM1 activity in various human cancers (Dimmer et al, 2008;Piao et al, 2009a;Li et al, 2015). Multiple human malignancies, including breast, colon, esophagus, lung, ovary, rectum, stomach, and uterine cervix, report high LETM1expression profile correlating with poor prognosis, low survival rates, upregulation of cancer stemness genes, and enhanced angiogenesis (Piao et al, 2009a(Piao et al, , 2019a(Piao et al, ,b, 2020Li et al, 2015Li et al, , 2020Wang et al, 2015Wang et al, , 2020Huang et al, 2017a;Yang et al, 2018). In thyroid, prostate, ovarian, and gastric cancers, LETM1 overexpression is correlated with increased cell survival via enhanced Akt signaling (Lee et al, 2016;Piao et al, 2020;Wang et al, 2020;Zhang et al, 2020).…”

Section: Letm1 In Cancermentioning

confidence: 99%

LETM1: A Single Entity With Diverse Impact on Mitochondrial Metabolism and Cellular Signaling

et al. 2021

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Nearly 2 decades since its discovery as one of the genes responsible for the Wolf-Hirschhorn Syndrome (WHS), the primary function of the leucine-zipper EF-hand containing transmembrane 1 (LETM1) protein in the inner mitochondrial membrane (IMM) or the mechanism by which it regulates mitochondrial Ca2+ handling is unresolved. Meanwhile, LETM1 has been associated with the regulation of fundamental cellular processes, such as development, cellular respiration and metabolism, and apoptosis. This mini-review summarizes the diversity of cellular functions impacted by LETM1 and highlights the multiple roles of LETM1 in health and disease.

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“…Among these genes, LBH promotes angiogenesis in glioma through VEGFA-mediated ERK signaling under hypoxic conditions (Jiang et al, 2019). LETM1 contributes to cancer cell proliferation and invasion via the PI3K/Akt signaling pathway and has been identified as a potential biomarker to predict the prognosis of gastric cancer and lung cancer (Piao et al, 2019;Li et al, 2020;Zhang et al, 2020). Additionally, LOX is considered to be a potential relapse marker for pancreatic cancer patients (Ma et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Prognostic Significance of Hsa-miR-100-5p and Its Related Gene Signature in Stomach Adenocarcinoma

Wang

Yang

et al. 2021

Front. Cell Dev. Biol.

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Stomach adenocarcinoma (STAD) is one of the most common cancers in the world. However, the prognosis of STAD remains poor, and the therapeutic effect of chemotherapy and immunotherapy varies from person to person. MicroRNAs (miRNAs) play vital roles in tumor development and metastasis and can be used for cancer diagnosis and prognosis. In this study, hsa-miR-100-5p was identified as the only dysregulated miRNA in STAD samples through an analysis of three miRNA expression matrices. A weighted gene co-expression network analysis (WGCNA) was performed to select hsa-miR-100-5p-related genes. A least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to establish a miR-100-5p-related prognostic signature. Kaplan–Meier analyses, nomograms, and univariate and multivariate Cox regression analyses were used to evaluate the prognostic signature, which was subsequently identified as an independent risk factor for STAD patients. We investigated the tumor immune environment between low- and high-risk groups and found that, among component types, M2 macrophages contributed the most to the difference between these groups. A drug sensitivity analysis suggested that patients with high-risk scores may be more sensitive to docetaxel and cisplatin chemotherapy and that patients in the low-risk group may be more likely to benefit from immunotherapy. Finally, external cohorts were evaluated to validate the robustness of the prognostic signature. In summary, this study may provide new ideas for developing more individualized therapeutic strategies for STAD patients.

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LETM1 is a potential biomarker that predicts poor prognosis in gastric adenocarcinoma

Cited by 15 publications

References 39 publications

Suppression of LETM1 inhibits the proliferation and stemness of colorectal cancer cells through reactive oxygen species–induced autophagy

Suppression of LETM1 inhibits the proliferation and stemness of colorectal cancer cells through reactive oxygen species–induced autophagy

LETM1: A Single Entity With Diverse Impact on Mitochondrial Metabolism and Cellular Signaling

Comprehensive Analysis of the Prognostic Significance of Hsa-miR-100-5p and Its Related Gene Signature in Stomach Adenocarcinoma

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