miR-98-5p inhibits gastric cancer cell stemness and chemoresistance by targeting branched-chain aminotransferases 1

Zhan, Panpan; Xiong, Shunbin; Chen, Meng; Sun, Lixin; Lan, Yu; Li, Jun; Sun, Lichao; Yang, Zhihua; Ran, Yuliang

doi:10.1016/j.lfs.2021.119405

Cited by 29 publications

(20 citation statements)

References 31 publications

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“…Among the candidate miRNAs, we are particularly interested in miR-98-5p. Meanwhile, miR-98-5p has been reported as a tumor suppressor gene to inhibit tumor growth and metastasis in a variety of cancers (Wu et al, 2019;Sun et al, 2020;Shi et al, 2021;Zhan et al, 2021), and associated with resistance to anti-tumor drug therapy (Wang et al, 2018). However, the relationship between miR-98-5p expression and Herceptin sensitivity has not been reported.…”

Section: Discussionmentioning

confidence: 99%

“…MiR-98-5p is a microRNA that can regulated mRNA translation. Many studies have found that miR-98-5p can regulate the expression of intracellular proteins and inhibit tumor proliferation (Qiu et al, 2020;Huang et al, 2021;Zhan et al, 2021). In this study, we screened the target genes of miR-98-5p by Target Scan, and IGF2 mRNA was one of them.…”

Section: Introductionmentioning

confidence: 97%

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MiR-98-5p/IGF2 Axis Influence Herceptin Sensitivity through IGF1R/HER2 Heterodimer Formation and AKT/mTOR Signal Pathway in HER2 Positive Breast Cancer

Zhang

Liu

2021

Asian Pac J Cancer Prev

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Background and Aim: IGF1R and HER2 are both members of the growth factor receptor family which is known to play a different role in breast cancer. However, correlation between IGF1R and HER2 has created a controversial situation that need to be fully delineated in development of Herceptin resistance. The aim of this study was to investigate the mechanism of Herceptin resistance through the IGF1R pathway in HER2 positive breast cancer. Materials and Methods: Clinical data were obtained from TCGA database and archived documents from The First Affiliated Hospital of Bengbu Medical College. Western blot and immunohistochemistry were used to detect proteins and their phosphorylation. Cell transfection were constructed using shRNA lentivirus vectors. RNAs were analyzed by RT-qPCR. Proteins in serum were analyzed by ELISA assay. Cell proliferation was analyzed by MTS method. Luciferase report experiment was conducted to verify RNA's inter-reaction. Results: Western blot showed IGF2 protein was significantly increased in Herceptin resistant SKBR3-R cells (P<0.01), and IGF1R/HER2 heterodimer level was significantly increased (P<0.01). Luciferase reporter assay verified miR-98-5p could bind to 3 'UTR of IGF2 mRNA. When miR-98-5p was upregulated, the expression level of IGF2 was decreased(P<0.01), the cell invasive ability was reduced(P<0.01), and ultimately, Herceptin resistant cells regained their sensitivity to Herceptin. In clinical research, we found that decreased miR-98-5p level or increased IGF2 level significantly associated with poor treatment response and poor overall survival (OS), poor recurrence free survival (RFS) and poor distant metastasis-free survival (DMFS) in HER2-positive breast cancer. Conclusion: MiR-98-5p and IGF2 might potential candidates for predicting Herceptin sensitivity and provides a new way to overcome Herceptin resistance in clinic.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

MiR-98-5p/IGF2 Axis Influence Herceptin Sensitivity through IGF1R/HER2 Heterodimer Formation and AKT/mTOR Signal Pathway in HER2 Positive Breast Cancer

Zhang

Liu

2021

Asian Pac J Cancer Prev

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“…Circ_0002874 expression is remarkably increased in the plasma of GC patients, and related to the tumor stage and lymph node metastasis. This circRNA achieves a high diagnostic power in separating GC patiets from non-cancer controls (AUC 0.836) (Sun X. et al, 2021). Circulating ncRNAs with potential diagnostic or prognostic role in GC are listed in Table 2.…”

Section: Ncrnas As Biomarkers In Gastric Cancermentioning

confidence: 99%

“…By contrast, the expression of miR-98 is decreased in CD44 + GCSCs. Elevated miR-98 expression inhibits the ability of self-renewal, tumorigenicity, and invasion of GCSCs by targeting BCAT1 ( Zhan et al, 2021 ). MiR-375 acts as a tumor-suppressive miRNA that reduces GC cell stemness primarily via triggering SLC7A11-dependent ferroptosis ( Ni et al, 2021 ).…”

Section: Biological Functions Of Ncrnas In Regulating the Hallmarks Of Gastric Cancermentioning

confidence: 99%

Non-Coding RNAs in Gastric Cancer: From Malignant Hallmarks to Clinical Applications

Chen

Shuai

et al. 2021

Front. Cell Dev. Biol.

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Gastric cancer (GC) is one of the most lethal malignancies worldwide. However, the molecular mechanisms underlying gastric carcinogenesis remain largely unknown. Over the past decades, advances in RNA-sequencing techniques have greatly facilitated the identification of various non-coding RNAs (ncRNAs) in cancer cells, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Accumulating evidence has revealed that ncRNAs are essential regulators in GC occurrence and development. However, ncRNAs represent an emerging field of cancer research, and their complex functionality remains to be clarified. Considering the lack of viable biomarkers and therapeutic targets in GC, further studies should focus on elucidating the intricate relationships between ncRNAs and GC, which can be translated into clinical practice. In this review, we summarize recent research progress on how ncRNAs modulate the malignant hallmarks of GC, especially in tumor immune escape, drug resistance, and stemness. We also discuss the promising applications of ncRNAs as diagnostic biomarkers and therapeutic targets in GC, aiming to validate their practical value for clinical treatment.

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“…Tumor suppressor miR-21 has also been found to enhance the sensitivity of GC cells to PTX, at least in part, by modulating P-glycoprotein expression ( 105 ). In addition, overexpression of miR-34a and miR-98 could sensitize GC cells to PTX by suppressing the expression of E2F5 and BCAT1, respectively ( 87 , 106 ).…”

Section: Implication Of Mirnas In Gc Drug Resistancementioning

confidence: 99%

Mechanisms of Action And Clinical Implications of MicroRNAs in the Drug Resistance of Gastric Cancer

Liu

et al. 2021

Front. Oncol.

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Gastric cancer (GC) is one of the most common malignant tumors of digestive systems worldwide, with high recurrence and mortality. Chemotherapy is still the standard treatment option for GC and can effectively improve the survival and life quality of GC patients. However, with the emergence of drug resistance, the clinical application of chemotherapeutic agents has been seriously restricted in GC patients. Although the mechanisms of drug resistance have been broadly investigated, they are still largely unknown. MicroRNAs (miRNAs) are a large group of small non-coding RNAs (ncRNAs) widely involved in the occurrence and progression of many cancer types, including GC. An increasing amount of evidence suggests that miRNAs may play crucial roles in the development of drug resistance by regulating some drug resistance-related proteins as well as gene expression. Some also exhibit great potential as novel biomarkers for predicting drug response to chemotherapy and therapeutic targets for GC patients. In this review, we systematically summarize recent advances in miRNAs and focus on their molecular mechanisms in the development of drug resistance in GC progression. We also highlight the potential of drug resistance-related miRNAs as biomarkers and therapeutic targets for GC patients.

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miR-98-5p inhibits gastric cancer cell stemness and chemoresistance by targeting branched-chain aminotransferases 1

Cited by 29 publications

References 31 publications

MiR-98-5p/IGF2 Axis Influence Herceptin Sensitivity through IGF1R/HER2 Heterodimer Formation and AKT/mTOR Signal Pathway in HER2 Positive Breast Cancer

MiR-98-5p/IGF2 Axis Influence Herceptin Sensitivity through IGF1R/HER2 Heterodimer Formation and AKT/mTOR Signal Pathway in HER2 Positive Breast Cancer

Non-Coding RNAs in Gastric Cancer: From Malignant Hallmarks to Clinical Applications

Mechanisms of Action And Clinical Implications of MicroRNAs in the Drug Resistance of Gastric Cancer

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