MicroRNA-421 regulated by HIF-1α promotes metastasis, inhibits apoptosis, and induces cisplatin resistance by targeting E-cadherin and caspase-3 in gastric cancer

Ge, Xiaoxiao; Liu, Xinyang; Lin, Feng; Li, Peng; Liu, Kaiyi; Geng, Ruixuan; Dai, Congqi; Lin, Ying; Tang, Wenbo; Wu, Zheng; Chang, Jinjia; Lu, Jianrong; Li, Jin

doi:10.18632/oncotarget.8228

Cited by 102 publications

(78 citation statements)

References 50 publications

(54 reference statements)

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“…The results suggested an association between miR-320 and HIF-1α in adjusting RB progression. Increasing evidence has shown that miRNA interfere with the metastasis and invasion of various types of cancer via the regulation of HIF-1α (21)(22)(23)(24). In this study, a luciferase reporter assay was employed to investigate the effect of miR-320 on HIF-1α.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-320 regulates autophagy in retinoblastoma by targeting hypoxia inducible factor-1α

Liang¹,

Chen²,

Zhu³

2017

Experimental and Therapeutic Medicine

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Abstract. Retinoblastoma (RB) is the most common malignancy in children. Due to refractory mechanisms of chemoresistance and the toxicity of chemotherapies, novel therapies for RB treatment are urgently required. MicroRNA-320 (miR-320) is believed to be associated with the tumorigenesis of RB, although the mechanism remains unclear. Considering the hypoxic intratumoral region, the roles of miR-320 and hypoxia inducible factor-1α (HIF-1α) in the regulation of autophagy were investigated in 30 human RB samples and WERI-RB1 cells. The results demonstrated that HIF-1α was the downstream target of miR-320, and decreased miRNA-320 or HIF-1α lead to the inhibition of autophagy in WERI-RB1 cells. Compared with WERI-RB1 cells that were not transfected, silenced HIF-1α caused a 1.41-fold increase (P<0.01) in p62, a 2.71-fold decrease of Beclin1, and inhibited miRNA-320. Silenced HIF-1α also resulted in 7.29-and 7.43-fold increases in phosphorylated-mechanistic target of rapamycin (mTOR) and mTOR, respectively. In conclusion, the present results suggest that miRNA-320 may regulate the development of autophagy by targeting HIF-1α and autophagy-related proteins in RB under hypoxic conditions.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-320 regulates autophagy in retinoblastoma by targeting hypoxia inducible factor-1α

Liang¹,

Chen²,

Zhu³

2017

Experimental and Therapeutic Medicine

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“…HIF‐1α is an important factor in the adaptation of cells to hypoxic environments by targeting different sets of genes . The involvement of HIF‐1α in CDDP resistance was previously demonstrated in several reports . Importantly, the Mxd1 gene has been shown to be activated specifically by HIF‐1α in colon cancer cells .…”

Section: Discussionmentioning

confidence: 90%

“…[36][37][38] The involvement of HIF-1α in CDDP resistance was previously demonstrated in several reports. 39,40 Importantly, the Mxd1 gene has been shown to be activated specifically by HIF-1α in colon cancer cells. 18 Our results show that blocking HIF-1α expression by siRNA significantly prevents hypoxia-induced Mxd1 up-regulation and sensitizes hypoxic U-2OS and MG-63 cells to CDDP.…”

Section: Discussionmentioning

confidence: 99%

Mxd1 mediates hypoxia‐induced cisplatin resistance in osteosarcoma cells by repression of the PTEN tumor suppressor gene

Zheng

Dong

et al. 2017

Molecular Carcinogenesis

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Hypoxia-induced chemoresistance remains a major obstacle to treating osteosarcoma effectively. Mxd1, a member of the Myc/Max/Mxd family, was shown to be involved in the development of drug resistance under hypoxia. However, the effect of Mxd1 on hypoxia-induced cisplatin (CDDP) resistance and its mechanism in osteosarcoma have not been fully elucidated. In this study, we demonstrated that HIF-1α-induced Mxd1 contributed to CDDP resistance in hypoxic U-2OS and MG-63 cells. The knockdown of Mxd1 expression elevated PTEN expression at both protein and RNA levels in these hypoxic cells. Using Luciferase reporter and ChIP assays, we confirmed that Mxd1 directly bound to the E-box sites within the PTEN promoter region. We further demonstrated that PTEN knockdown decreased CDDP sensitivity in Mxd1 siRNA-transfected U-2OS and MG-63 cells under hypoxia. Our results also showed that Mxd1 deficiency in hypoxic U-2OS and MG-63 cells lead to inactivation of PI3K/AKT signaling, which is the downstream of PTEN. Furthermore, blockade of PI3K/AKT signal re-sensitized hypoxic U-2OS and MG-63 cells to CDDP. Taken together, these findings suggest that HIF-1α-induced Mxd1 up-regulation suppresses the expression of PTEN under hypoxia, which leads to the activation of PI3K/AKT antiapoptotic and survival pathway. As a result CDDP resistance in osteosarcoma cells is induced.

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“…Moreover, Li et al validated that miRNA‐148a‐3p suppressed the cellular‐protective autophagy in cisplatin‐resistant GC cells by activating mTORC1 activity and inhibiting RAB12 expression . The expression level of miR‐421 in GC cells is upregulated via HIF‐1α and it promotes DDP resistance through E‐cadherin and caspase‐3 . The miR‐218 promoted the chemosensitivity of GC cells to DDP via its target mTOR, and miR‐218 inhibits MDR of GC cells by targeting Hedgehog/smoothened .…”

Section: Mirnas and Drug Resistance In Gcmentioning

confidence: 99%

Dysregulation of miRNAs as a signature for diagnosis and prognosis of gastric cancer and their involvement in the mechanism underlying gastric carcinogenesis and progression

Ahadi

2020

IUBMB Life

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Gastric cancer (GC) is the second main cause of cancer‐related mortality worldwide. The poor prognosis and survival of GC are due to diagnosis in an advanced, noncurable stage and with a restricted response to chemotherapy. GC is usually monitored in an advanced stage; therefore, the poor prognosis and lower level of survival rate with a restricted response to chemotherapy can be detected. Valuable and sensible biomarkers are urgently needed to display screen patients with a high risk of GC that can complement endoscopic diagnosis. Such biomarkers will enable the efficient prediction of the therapeutic response and prognosis of GC patients and prefer the establishment of an advantageous treatment method for each and every patient. Noninvasive diagnostic biomarkers may additionally make a contribution to the early identification of GC and enhance medical management. MicroRNAs (miRNAs) are a group of small noncoding RNAs that have displayed a strong association with GC. Accumulating evidence indicates that miRNAs are potential biomarkers with more than one diagnostic function for GC. Actually, miRNAs regulate cell proliferation, apoptosis, migration, invasion, and metastasis via many biological pathways through the repression of target mRNAs. The current review is accordingly to spotlight the multifaceted roles of miRNAs in GC, which would provide indications for future research. Therefore, we review right here the aberrant expression of miRNAs and underlying mechanisms, consequent effects due to miRNAs dysregulation, and accountable target genes in GC. Besides, potential clinical applications are also highlighted.

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MicroRNA-421 regulated by HIF-1α promotes metastasis, inhibits apoptosis, and induces cisplatin resistance by targeting E-cadherin and caspase-3 in gastric cancer

Cited by 102 publications

References 50 publications

MicroRNA-320 regulates autophagy in retinoblastoma by targeting hypoxia inducible factor-1α

MicroRNA-320 regulates autophagy in retinoblastoma by targeting hypoxia inducible factor-1α

Mxd1 mediates hypoxia‐induced cisplatin resistance in osteosarcoma cells by repression of the PTEN tumor suppressor gene

Dysregulation of miRNAs as a signature for diagnosis and prognosis of gastric cancer and their involvement in the mechanism underlying gastric carcinogenesis and progression

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