The Prominent Role of HMGA Proteins in the Early Management of Gastrointestinal Cancers

Costa, Nathalia Meireles Da; Pinto, Luís Felipe Ribeiro; Nasciutti, Luiz Eurico; Palumbo, Antônio

doi:10.1155/2019/2059516

Cited by 6 publications

(7 citation statements)

References 72 publications

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“…Finally, we elucidated the oncogenic mechanism of GRP75 and HMGA1 in LUAD progression. The oncogenic role and therapeutic potential of GRP75 or HMGA1 have been reported in several cancers 28–30 . Consistently, the present study results also show that both GRP75 and HMGA1 play oncogenic roles in LUAD and exhibit potential as therapeutic targets in LUAD.…”

Section: Discussionsupporting

confidence: 91%

GRP75‐mediated upregulation of HMGA1 stimulates stage I lung adenocarcinoma progression by activating JNK/c‐JUN signaling

Qiao

Wang

et al. 2021

Thoracic Cancer

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Background Recurrence is a major challenge in early‐stage lung adenocarcinoma (LUAD) treatment. Here, we investigated the role and mechanism of high‐mobility group AT‐hook 1 (HMGA1) and glucose‐regulated protein 75‐kDa (GRP75) in stage I LUAD and evaluated their potential as biomarkers for predicting the recurrence and prognosis of stage I LUAD. Methods The TCGA dataset was used to investigate the clinical significance of HMGA1 and GRP75 in early‐stage LUAD. The biological functions of HMGA1 and GRP75 in LUAD were investigated both in vitro and in vivo through overexpression and knockdown experiments. The interaction and regulation between HMGA1 and GRP75 were evaluated with coimmunoprecipitation and ubiquitination assays. The downstream signaling pathway of the GRP75/HMGA1 axis was investigated by mRNA‐sequencing analysis. Results Both HMGA1 expression levels and GRP75 expression levels were associated with recurrence in stage I LUAD patients. In particular, HMGA1 had potential as an independent prognostic factor in stage I LUAD patients. Overexpression of GRP75 or HMGA1 significantly stimulated LUAD cell growth and metastasis, while silencing GRP75 or HMGA1 inhibited LUAD cell growth and metastasis in vitro and in vivo. Importantly, GRP75 inhibited ubiquitination‐mediated HMGA1 degradation by directly binding to HMGA1, thereby causes HMGA1 upregulation in LUAD. In addition, the GRP75/HMGA1 axis played its role by activating JNK/c‐JUN signaling in LUAD. Conclusions The activation of GRP75/HMGA1/JNK/c‐JUN signaling is an important mechanism that promotes the progression of stage I LUAD, and a high level of HMGA1 is a novel biomarker for predicting recurrence and a poor prognosis in stage I LUAD patients.

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Section: Discussionsupporting

confidence: 91%

GRP75‐mediated upregulation of HMGA1 stimulates stage I lung adenocarcinoma progression by activating JNK/c‐JUN signaling

Qiao

Wang

et al. 2021

Thoracic Cancer

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“…Among the target genes of miR-635, HMGA1, a small nuclear protein belonging to the HMGA family, is an oncofoetal gene and regulates genesis and development of various neoplasms [ 32 ]. Interestingly, HMGA1 displays a critical role in the detection and progression of gastrointestinal tumors [ 33 ]. HMGA family members are considered reliable biomarkers able to efficiently track a gastrointestinal tumor in the future [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Asiaticoside Suppresses Gastric Cancer Progression and Induces Endoplasmic Reticulum Stress through the miR-635/HMGA1 Axis

Zhang

Chen³

et al. 2022

Journal of Immunology Research

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Objective. Gastric cancer is a prevalent malignant tumor with high morbidity and poor prognosis. Asiaticoside (AC) has antitumor effects, while its role in gastric cancer is elusive. Thus, this study investigated the effect of AC on gastric cancer progression. Methods. Cell viability and migration were determined using the CCK-8 and Transwell migration assay. Endoplasmic reticulum stress was detected through measuring the expressions of GRP78, Chop, and hnRNPA1 by Western blot. The luciferase assay confirmed the relationship between miR-635 and High Mobility Group AT-Hook 1 (HMGA1). The effect of AC on tumor growth was evaluated by establishing a xenograft tumor. The survival rate of mice was analyzed by Kaplan-Meier analysis. Results. AC suppressed gastric cancer cell viability and restrained cell migration. AC inhibited the expressions of the cell proliferation marker PCNA and EMT-related marker N-cadherin and increased E-cadherin expression. AC elevated the levels of GRP78 and Chop and suppressed the level of hnRNPA1. In addition, AC restrained gastric cancer proliferation and migration ability and induced endoplasmic reticulum stress by upregulating miR-635 expression. Furthermore, HMGA1 was proven to be a target of miR-635. AC constrained gastric cancer cell proliferation and migration and promoted endoplasmic reticulum stress by regulating HMGA1. Moreover, AC suppressed in vivo tumor growth and improved the survival time of mice. Additionally, AC elevated the expressions of miR-635, E-cadherin, GRP78, and Chop and inhibited Ki-67, HMGA1, N-cadherin, and hnRNPA1 expressions in tumor tissues of mice. Conclusion. AC suppressed gastric cancer progression and induced endoplasmic reticulum stress via the miR-635/HMGA1 axis, providing a valuable drug against gastric cancer.

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“…In China, the incidence of gastric cancer ranks 2nd among all the malignancies, just below lung cancer. And it is still the 3rd leading cause of cancer-related deaths [ 1 ]. There are approximately 1.2 million newly diagnosed cases of gastric cancer worldwide, 40% of which came from China.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Influencing Factors on the Occurrence and Development of Gastric Cancer in High-Incidence Areas of Digestive Tract Tumors Based on High Methylation of GPX3 Gene

Xie

Jian-min

2022

Journal of Oncology

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Stomach cancer is the second largest cause of cancer-related mortality globally, and it continues to be a reason for worry today. Inhalation of the stomach cancer risk factor H. pylori produces large levels of reactive oxygen species (ROS). When combined with glutathione reductase, glutathione peroxidase 3 (GPX3) catalyzes the reduction of hydrogen peroxide and lipid peroxides. To get a better understanding of the GPX3 gene’s role in the illness, the researchers used quantitative real-time RT-PCR to examine the gene’s expression and regulation in gastric cancer cell lines, original gastric cancer samples, and 45 normal stomach mucosa adjacent to malignancies. According to the research, GPX3 expression was decreased or silenced in eight of nine cancer cell lines and 83 percent of gastric cancer samples (90/108) as compared to normal gastric tissues in the vicinity of the tumor ( P < 0.0001 ). It was found that 60 percent of stomach cancer samples exhibited DNA hypermethylation after analyzing the GPX3 promoter ( P = 0.007 ) (a methylation level of more than 10 percent, as measured by bisulfite pyrosequencing). In stomach tumors, we found a statistically significant reduction in the amount of GPX3 DNA copies ( P < 0.001 ). The gene expression of SNU1 and MKN28 cells was restored after treatment with 5-Aza-2′ Deoxycytidine to reduce GPX3 promoter methylation. Genetic and epigenetic alterations lead GPX3 to be dysfunctional in gastric cancer. This indicates that the systems that regulate ROS have been disrupted, and GPX3 may be implicated in the development of gastric cancer, as shown by our results when evaluated alone and in combination.

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The Prominent Role of HMGA Proteins in the Early Management of Gastrointestinal Cancers

Cited by 6 publications

References 72 publications

GRP75‐mediated upregulation of HMGA1 stimulates stage I lung adenocarcinoma progression by activating JNK/c‐JUN signaling

GRP75‐mediated upregulation of HMGA1 stimulates stage I lung adenocarcinoma progression by activating JNK/c‐JUN signaling

Asiaticoside Suppresses Gastric Cancer Progression and Induces Endoplasmic Reticulum Stress through the miR-635/HMGA1 Axis

Analysis of Influencing Factors on the Occurrence and Development of Gastric Cancer in High-Incidence Areas of Digestive Tract Tumors Based on High Methylation of GPX3 Gene

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