TIPRL, a Novel Tumor Suppressor, Suppresses Cell Migration, and Invasion Through Regulating AMPK/mTOR Signaling Pathway in Gastric Cancer

Luan, Meng; Shi, Shanshan; Shi, Duan-Bo; Liu, Haiting; Ma, Ran-Ran; Xu, Xiaoqun; Sun, Yujing; Gao, Peng

doi:10.3389/fonc.2020.01062

Cited by 10 publications

(11 citation statements)

References 53 publications

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“…Studies from the GEO database ( ) were considered eligible according to the following criteria: i) Studies with GC tissue samples; ii) studies with information on technology and platform used for studies. Based on these criteria, the GSE58828, GSE72305 ( 12 ) and GSE99416 ( 13 ) GC datasets were downloaded from the GEO database ( 14 ). Details of each microarray study are presented in Table I .…”

Section: Methodsmentioning

confidence: 99%

Integrative analysis of the gastric cancer long non‑coding RNA‑associated competing endogenous RNA network

Jiang

Zhang

et al. 2021

Oncol Lett

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Gastric cancer (GC) is a common type of cancer, and identification of novel diagnostic biomarkers associated with this disease is important. The present study aimed to identify novel diagnostic biomarkers associated with the prognosis of GC, using an integrated bioinformatics approach. Differentially expressed long non-coding RNAs (lncRNAs) associated with GC were identified using Gene Expression Omnibus datasets (GSE58828, GSE72305 and GSE99416) and The Cancer Genome Atlas database. A competing endogenous RNA network that incorporated five lncRNAs [long intergenic non-protein coding RNA 501 (LINC00501), LINC00365, SOX21 antisense divergent transcript 1 (SOX21-AS1), GK intronic transcript 1 (GK-IT1) and DLEU7 antisense RNA 1 (DLEU7-AS1)], 29 microRNAs and 114 mRNAs was constructed. Gene Ontology and protein-protein interaction network analyses revealed that these lncRNAs may be involved in ‘biological regulation’, ‘metabolic process’, ‘cell communication’, ‘developmental process’, ‘cell proliferation’, ‘reproduction’ and the ‘cell cycle’. The results of receiver operating characteristic curve analysis demonstrated that LINC00501 (AUC=0.819), LINC00365 (AUC=0.580), SOX21-AS1 (AUC=0.736), GK-IT1 (AUC=0.823) and DLEU7-AS1 (AUC=0.932) had the potential to become valuable diagnostic biomarkers for GC. Associations with clinicopathological characteristics demonstrated that LINC00501 expression was significantly associated with sex (P=0.015) and tumor grade (P=0.022). Furthermore, LINC00365 expression was significantly associated with lymph node metastasis (P=0.025). Gene set enrichment analysis revealed that LINC00501, LINC00365 and SOX21-AS1 were enriched in signaling pathways associated with GC. Reverse transcription-quantitative PCR analysis demonstrated that LINC00501 expression (P=0.043) was significantly upregulated in GC tissues, whereas the expression levels of LINC00365 (P=0.033) and SOX21-AS1 (P=0.037) were significantly downregulated in GC tissues. Taken together, the results of the present study suggest that LINC00501, LINC00365, SOX21-AS1, GK-IT1 and DLEU7-AS1 may be used as novel diagnostic biomarkers for GC, and may be functionally associated with GC development and progression.

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Section: Methodsmentioning

confidence: 99%

Integrative analysis of the gastric cancer long non‑coding RNA‑associated competing endogenous RNA network

Jiang

Zhang

et al. 2021

Oncol Lett

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“…При проведении корреляционного анализа были выявлены ассоциации между изучаемыми молекулярными маркерами, свидетельствующие о влиянии АМРК на состояние основных компонентов изучаемого внутриклеточного каскада. Известно, что активация AMPK может сопровождаться фосфорилированием mTOR, p70S6K и 4E-BP1, способствуя снижению интенсивности основных процессов онкогенеза в культуре клеток РЖ [5]. Также выявлено, что развитие резистентности при РЖ связано с активацией АМРК и ингибированием компонентов АKT/ mTOR сигнального каскада [6,14].…”

Section: Discussionunclassified

“…Показано, что изначально высокие уровни экспрессии 4EBP, mTOR, AMPK ассоциированы с регрессией опухоли и ее чувствительностью к неоадъювантной терапии. Вероятно, это объясняется их ролью в формировании биологического поведения опухоли, что подтверждается ранее представленными данными [5,6]. Resume: Introduction.…”

Section: Discussionunclassified

“…Выявлены неоднозначные данные о роли AMPK в онкогенезе. Известно, что активация данной протеинкиназы может сопровождаться развитием противоопухолевого эффекта [5]. Также имеются сведения, что АМРК связана с развитием резистентности к химиотерапевтическому лечению при РЖ [6].…”

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Influence of neoadjuvant therapy on the expression of molecular markers in gastric cancer

et al. 2020

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Резюме: Рак желудка (РЖ) остается одной из ведущих причин смерти от злокачественных новообразований. Известно, что его патогенез представляет собой многоступенчатый и гетерогенный процесс с широким спектром генетических изменений. Среди ведущих механизмов выделяют нарушение регуляции важнейших сигнальных путей клетки, что определяет нарушения клеточного цикла, дифференцировки клеток, процессов репарации ДНК, апоптоза и ведет к развитию злокачественной опухоли.Цель работы: исследование экспрессии компонентов AKT/m-TOR сигнального пути и AMPK в ткани опухоли у больных раком желудка на фоне химиотерапии по схеме FLOT.Материалы и методы. В исследование было включено 24 больных раком желудка. Пациенты получали комбинированное лечение, включающее неоадъювантную химиотерапию по схеме FLOT, хирургическое вмешательство. Материалом исследования была нормальная и опухолевая ткань, полученная при проведении диагностической гастроскопии у пациентов. Уровень мРНК изучаемых показателей определялся методом ПЦР в реальном времени.Результаты и их обсуждение. Значимые изменения происходили при исследовании уровня показателей после лечения. Отмечено, что на фоне неадъювантной терапии происходит снижение экспрессии 4EBP1 в 2,2 раза по сравнению с его уровнем до начала лечения. При этом эффект лечения был связан с комплексом показателей, позволяющих предсказывать его еще до начала комбинированной терапии. Отмечено снижение экспрессии 4EBP, mTOR и AMPK по мере уменьшения эффекта терапии в группах пациентов с полной регрессией, частичной регрессией, стабилизацией и прогрессированием заболевания.

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“…In gastric cancer development, these molecular parameters play an ambiguous role, which is still not fully understood. It is known that the activation of protein kinase AMPK can be accompanied by the development of an antitumor effect, which is accompanied by an increase in the sensitivity of the tumor to treatment [Luan M, 2020]. There is also evidence that AMPK is associated with the development of resistance to chemotherapy treatment in gastric cancer [Park JB 2018].…”

Section: Introductionmentioning

confidence: 99%

Title: Expression and content of the LC3B protein in gastric cancers, relationship to mTOR, AMPK expression, clinical and morphological parameters, and the tumor response to neoadjuvant chemotherapy

Spirina¹,

Августинович²,

Bakina³

et al. 2021

Preprint

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Background. Autophagy plays a dual role in oncogenesis processes. On the one hand, increasing the cell's resistance to oncogenic factors, and on the other hand, participating in the processes of tumor progression and the formation of resistance to antitumor treatment. It has been shown that autophagy correlates with the aggressive course of the disease and its poor prognosis. The molecular cascades that regulate autophagy are numerous and varied and play a role in tumorigenesis that has not yet been studied.The study aimed to study the expression of LC3B, mTOR, AMPK, the content of the LC3B protein in gastric cancer tissue, and its relationship with disease progression, and the response to anti-cancer therapy.Material and methods. The study included 34 patients with morphologically verified gastric cancer. All patients were hospitalized in the Department of Abdominal Oncology of the TNIMTs Research Institute of Oncology. All patients had FLOT neoadjunvant chemotherapy (NACT) (fluorouracil, leucovorin, oxaliplatin, and docetaxel) followed the gastrectomy. The response to the combined treatment of patients was evaluated according to the RECIST 1.1 criteria.The study's material was the non-transformed and tumor tissues obtained during diagnostic video gastroscopy in patients before the start of combined treatment and after surgical treatment, frozen after collection and stored at t -800C. The expression of LC3B, mTOR, AMPK was determined by real-time PCR, the LC3B protein level - using the Western Blotting method.Results and their discussion. The mRNA level and the content of the LC3B protein are associated with the size of the tumor, damage to regional lymph nodes (spread of the disease), and the presence of cricoid cells. The AMPK mRNA level increased in patients with the T4N0-2M0 stage in 37.7 and 7.33 times, respectively, compared with patients with the T2N0M0 and T3N0-1M0 stages. The opposite character in mTOR, AMPK changes in the GCs before anti-cancer therapy is noted. At the same time, the local prevalence of the tumor and the lesion of regional lymph nodes were associated with a decrease in mTOR mRNA level.A decrease in mTOR expression is accompanied by an increase in AMPK expression in a gastric tumor. It is associated, first of all, with the clinical and morphological parameters of the primary process. mTOR expression is reduced in patients with a higher local prevalence of the process; in contrast, AMPK grows with tumor size.There is an increase in the LC3B expression, which, probably, can determine the response to therapy. As a result of the study, an increase in LC3B mRNA before the start of treatment and the concentration of autophagy protein after NACT with a decrease in therapy effectiveness was recorded. An increase in the protein level in patients with partial regression and stabilization of the tumor process by 3.65 and 5.78 times compared with patients with complete tumor regression was noted. Conclusion. The development of the disease and the prediction of anticancer therapy's effectiveness is directly related to the expression level of LC3B, mTOR, and AMPK. The following relationship was revealed: a decrease in mTOR expression and an increase in the level of mRNA and protein LC3B, AMPK expression combined with the progression of the disease in the form of the development of distant metastases, as well as the predicted future low effectiveness of NACT.

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TIPRL, a Novel Tumor Suppressor, Suppresses Cell Migration, and Invasion Through Regulating AMPK/mTOR Signaling Pathway in Gastric Cancer

Cited by 10 publications

References 53 publications

Integrative analysis of the gastric cancer long non‑coding RNA‑associated competing endogenous RNA network

Integrative analysis of the gastric cancer long non‑coding RNA‑associated competing endogenous RNA network

Influence of neoadjuvant therapy on the expression of molecular markers in gastric cancer

Title: Expression and content of the LC3B protein in gastric cancers, relationship to mTOR, AMPK expression, clinical and morphological parameters, and the tumor response to neoadjuvant chemotherapy

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