miR-449a enhances radiosensitivity through modulating pRb/E2F1 in prostate cancer cells

Mao, Aihong; Liu, Yang; Wang, Yali; Zhao, Qian; Zhou, Xin; Sun, Chao; Chen, Di; Si, Jing; Gan, Lu; Zhang, Hong

doi:10.1007/s13277-015-4336-8

Cited by 30 publications

(20 citation statements)

References 39 publications

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“…Using an antagomir (anti-miR-449a), miR-499a expression was suppressed and increased cell proliferation was observed [48]. Conversely, after over-expressing miR-449a in PC-3 and DU145 cells using a plasmid construct, cell cycle arrest was observed [47]. Collectively, these results support the hypothesis that miR-499a is involved in cell cycle arrest, which impacts radiosensitivity.…”

Section: Mirnas In Cell Cycle Progression After Radiationsupporting

confidence: 55%

“…c-Myc, which controls Cdc25A expression, is also observed as a target of miR-449a. Surprisingly, in the first publication by Mao et al, miR-449a is decreased in PCa DU145 and PC-3 cell lines after IR [47], but in a following publication, they reported that miR-499a is up-regulated in the LNCaP cell line following IR [48]. Thus, miRNA expression effects may be cell-line dependent, with downregulation of miR-449a in androgen-dependent prostate cells inducing radioresistance via alterations in cell cycle arrest.…”

Section: Mirnas In Cell Cycle Progression After Radiationmentioning

confidence: 98%

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microRNAs identified in prostate cancer: Correlative studies on response to ionizing radiation

et al. 2020

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As the most frequently diagnosed non-skin cancer in men and a leading cause of cancer-related death, understanding the molecular mechanisms that drive treatment resistance in prostate cancer poses a significant clinical need. Radiotherapy is one of the most widely used treatments for prostate cancer, along with surgery, hormone therapy, and chemotherapy. However, inherent radioresistance of tumor cells can reduce local control and ultimately lead to poor patient outcomes, such as recurrence, metastasis and death. The underlying mechanisms of radioresistance have not been fully elucidated, but it has been suggested that miRNAs play a critical role. miRNAs are small non-coding RNAs that regulate gene expression in every signaling pathway of the cell, with one miRNA often having multiple targets. By fine-tuning gene expression, miRNAs are important players in modulating DNA damage response, cell death, tumor aggression and the tumor microenvironment, and can ultimately affect a tumor's response to radiotherapy. Furthermore, much interest has focused on miRNAs found in biofluids and their potential utility in various clinical applications. In this review, we summarize the current knowledge on miRNA deregulation after irradiation and the associated functional outcomes, with a focus on prostate cancer. In addition, we discuss the utility of circulating miRNAs as non-invasive biomarkers to diagnose, predict response to treatment, and prognosticate patient outcomes.

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Section: Mirnas In Cell Cycle Progression After Radiationsupporting

confidence: 55%

Section: Mirnas In Cell Cycle Progression After Radiationmentioning

confidence: 98%

microRNAs identified in prostate cancer: Correlative studies on response to ionizing radiation

et al. 2020

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“…In this regard, recent evidence confirms our findings in lung cancer 57 which supports the universal character of our observations. However, other putative targets of those microRNA should be taken into account, and also their relationship with E2F1-RB 58 , in order to describe a possible feedback loop that could be regulating each member.…”

Section: Discussionmentioning

confidence: 99%

CHK1 expression in Gastric Cancer is modulated by p53 and RB1/E2F1: implications in chemo/radiotherapy response

Bargiela-Iparraguirre

Prado-Marchal

Fernández-Fuente

et al. 2016

Sci Rep

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Radiation has a limited but relevant role in the adjuvant therapy of gastric cancer (GC) patients. Since Chk1 plays a critical function in cellular response to genotoxic agents, we aimed to analyze the role of Chk1 in GC as a biomarker for radiotherapy resistance. We analyzed Chk1 expression in AGS and MKN45 human GC cell lines by RT-QPCR and WB and in a small cohort of human patient’s samples. We demonstrated that Chk1 overexpression specifically increases resistance to radiation in GC cells. Accordingly, abrogation of Chk1 activity with UCN-01 and its expression with shChk1 increased sensitivity to bleomycin and radiation. Furthermore, when we assessed Chk1 expression in human samples, we found a correlation between nuclear Chk1 accumulation and a decrease in progression free survival. Moreover, using a luciferase assay we found that Chk1’s expression is controlled by p53 and RB/E2F1 at the transcriptional level. Additionally, we present preliminary data suggesting a posttranscriptional regulation mechanism, involving miR-195 and miR-503, which are inversely correlated with expression of Chk1 in radioresistant cells. In conclusion, Chk1/microRNA axis is involved in resistance to radiation in GC, and suggests Chk1 as a potential tool for optimal stratification of patients susceptible to receive adjuvant radiotherapy after surgery.

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“…In addition, Zhang et al . demonstrated that upregulation of miR‐449a strengthened prostate cancer cell radiosensitivity in relation to ionizing radiation and enhanced apoptosis by targeting the pRb/E2F1 pathway . Therefore, we suggest that SNHG7 could interact with miR‐449a to modulate NSCLC progression.…”

Section: Discussionmentioning

confidence: 79%

Long noncoding RNA SNHG7 contributes to cell proliferation, migration, invasion and epithelial to mesenchymal transition in non‐small cell lung cancer by regulating miR‐449a/TGIF2 axis

et al. 2019

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Background: Non-small cell lung cancer (NSCLC) is an intractable malignant lung cancer with high rates of metastasis and mortality. Currently, long noncoding RNA nuclear RNA host gene 7 (SNHG7) is recognized as a biomarker of multiple cancers. However, the role of SNHG7 in NSCLC requires further understanding. Methods: The expression of SNHG7, miR-449a and TGIF2 in NSCLC tumors and cells was examined by quantitative real time polymerase chain reaction (qRT-PCR). Cell viability was measured by MTT assay. Cell migration and invasion was conducted using transwell assay. Protein expression of TGIF2, vimentin, N-cadherin and E-cadherin was detected by western blot. The interaction between miR-449a and SNHG7 or TGIF2 was determined by luciferase reporter system, RIP and RNA pull-down assay, respectively. Xenograft mice models were established by subcutaneously injecting A549 cells transfected with sh-SNHG7 and sh-control. Results: SNHG7 expression was upregulated in NSCLC tumors and cells compared with normal tissues and cells. SNHG7 silencing repressed cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT) in NSCLC. Consistently, SNHG7 knockdown hindered tumor growth in vivo. The subsequent luciferase reporter system, RIP and RNA pull-down assay validated the interaction between miR-449a and SNHG7 or TGIF2. The rescue experiments displayed that miR-449a inhibitor counteracted SNHG7 silencing induced inhibition on proliferation, migration, invasion and EMT. Similarly, restoration of TGIF2 reversed miR-449a mediated inhibition on cell progression. In addition, the results indicated that SNHG7 could regulate cell progression by targeting miR-449a/TGIF2 axis. Conclusion: SNHG7 contributed to cell proliferation, migration, invasion and EMT in NSCLC by upregulating TGIF2 via sponging miR-449a, representing a novel targeted therapy method for NSCLC.

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miR-449a enhances radiosensitivity through modulating pRb/E2F1 in prostate cancer cells

Cited by 30 publications

References 39 publications

microRNAs identified in prostate cancer: Correlative studies on response to ionizing radiation

microRNAs identified in prostate cancer: Correlative studies on response to ionizing radiation

CHK1 expression in Gastric Cancer is modulated by p53 and RB1/E2F1: implications in chemo/radiotherapy response

Long noncoding RNA SNHG7 contributes to cell proliferation, migration, invasion and epithelial to mesenchymal transition in non‐small cell lung cancer by regulating miR‐449a/TGIF2 axis

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