miR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic Cancer

Xia, Jun; Cao, Tong; Ma, Cong; Shi, Ying; Sun, Yu; Wang, Z. Peter; Ma, Jia

doi:10.1016/j.omtn.2018.08.012

Cited by 48 publications

(44 citation statements)

References 36 publications

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“…Studies on miR-7 have been conducted in different types of tumors, and its function as a tumor suppressor has been demonstrated in pancreatic cancer (25) and glioma (26). In VSMCs derived from AAA in the present study, miR-7 suppressed proliferation and promoted the generation of ROS as well as LDH activity.…”

Section: Discussionsupporting

confidence: 48%

CDR1as/miR‑7/CKAP4 axis contributes to the pathogenesis of abdominal aortic aneurysm by regulating the proliferation and apoptosis of primary vascular smooth muscle cells

2020

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Abdominal aortic aneurysm (AAA) is characterized as dilation of the aortic wall. Dysregulation of vascular smooth muscle cells (VSMCs) can contribute to the development of this phenotype. Circular RNAs and microRNAs (miRNAs) can regulate the proliferation and apoptosis of VSMCs. This present study aimed to identify the mechanisms of action behind the regulation of cerebellar degeneration-related protein 1 antisense RNA (CDR1as)/miRNA (miR)-7 in VSMCs. The expression levels of miR-7 were upregulated, whereas the levels of CDR1as and cytoskeleton-associated protein 4 (CKAP4) were downregulated in aortic specimens obtained from 10 patients who underwent surgery for AAA compared with aortic specimens from 10 control patients who underwent coronary artery bypass surgery. The molecular mechanism of action of CDR1as/miR-7 was investigated in primary VSMCs. The results of Cell Counting kit-8 and cell growth curve assays revealed that overexpression of CDR1as and knockdown of miR-7, increased VSMC proliferation, whereas knockdown of CDR1as and overexpression of miR-7 suppressed VSMC proliferation. In addition, overexpression of CDR1as and knockdown of miR-7, suppressed apoptosis in VSMCs, indicated by the decreased levels of reactive oxygen species (ROS) and lactate dehydrogenase (LDH) activity, whereas knockdown of CDR1as and overexpression of miR-7 exhibited the opposite effects. The results of luciferase reporter and biotin pull-down assays confirmed that CDR1as directly bound to miR-7 and suppressed its expression. Additionally, the CDR1as-induced proliferation and suppressed apoptosis was reversed by the overexpression of miR-7. Furthermore, luciferase reporter, reverse transcription-quantitative PCR and western blot assays revealed that miR-7 directly targeted CKAP4 and suppressed its expression. Additionally, the miR-7-suppressed proliferation and increased ROS and LDH activity were reversed by the overexpression of CKAP4. CDR1as also decreased caspase 3/7 activity, which was reversed by miR-7 mimics. miR-7 increased the activity of caspase 3/7, which was again reversed by the overexpression of CKAP4. Therefore, CDR1as, miR-7 and CKAP4 may act in the same pathway to regulate VSMC proliferation and apoptosis.

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Section: Discussionsupporting

confidence: 48%

CDR1as/miR‑7/CKAP4 axis contributes to the pathogenesis of abdominal aortic aneurysm by regulating the proliferation and apoptosis of primary vascular smooth muscle cells

2020

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“…miR-214 promoted radiosensitivity by inhibiting autophagy that was mediated by autophagy-related gene 12 (ATG12) in colorectal cancer ( 35 ). In recent years, several studies have demonstrated that miR-7 plays an antitumor role in tumorigenesis, including pancreatic ( 36 ), lung ( 7 ), thyroid ( 37 ), and gastric cancer ( 38 ). Concurrently, miR-7 has been revealed to reduce the levels of EGFR and AKT by activating the EGFR/PI3K/AKT signaling pathway, which delays radiation-induced DNA DSBs and increases the radiosensitivity of A549 cells, laryngeal squamous cell carcinoma SQ20B cells, breast cancer MDA-MB-468 cells and malignant glioma U251 and U87 cells ( 9 ).…”

Section: Discussionmentioning

confidence: 99%

miR‑7/SP1/TP53BP1 axis may play a pivotal role in NSCLC radiosensitivity

et al. 2020

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MicroRNA-7 (miR-7) has been identified as a tumor suppressor in non-small cell lung cancer (NSCLC) and a radiosensitivity regulator. Numerous studies have revealed that specific protein 1 (SP1) plays a critical role in the tumorigenesis of various types of cancers and regulates radiosensitivity and tumor suppressor p53-binding protein 1 (TP53BP1), which plays an essential role in DNA repair. However, it is not clear whether miR-7 has a regulatory effect on SP1 and TP53BP1 in NSCLC. In the present study it was revealed that miR-7 directly binds to the 3′UTR of SP1, thereby suppressing SP1 expression to regulate radiosensitivity. Overexpression of miR-7 and SP1 and knockdown of miR-7 and SP1 were performed using lentiviral transfection. Protein and mRNA abundance of SP1 and TP53BP1 were determined using western blotting and RT-qPCR, respectively, while miR-7 binding to SP1 was validated using a luciferase reporter assay. Biological function analysis indicated that miR-7 negatively regulated SP1 and inhibited cell proliferation, migration, and invasion when combined with radiation. It was also revealed that the expression of TP53BP1 was positively regulated by SP1 or negatively regulated by miR-7. In conclusion, SP1 was a target of miR-7, and the decreased expression of SP1 resulting from miR-7 overexpression in NSCLC was vital for improving radiosensitivity in NSCLC cells. Moreover, SP1 expression was detected in 95 paired NSCLC and adjacent normal tissues, and it was determined that SP1 was significantly upregulated in NSCLC tissues and that its upregulation was correlated with the degree of tissue differentiation. Thus, SP1 and/or miR-7 may be potential molecular targets in NSCLC radiotherapy.

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“…Recently, miR-7 has been reported to play an important role in regulating the biological process of various diseases [46,47]. For instance, miR-7 is a tumor suppressor and increase cisplatin sensitivity of gastric cancer cells by targeting mTOR, indicating its potential application for the treatment of human gastric cancer in the future [48].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-7, synergizes with RORα, negatively controls the pathology of brain tissue inflammation

Yue

Zhao

Chen

et al. 2020

J Neuroinflammation

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Background: Accumulating evidence has documented that microRNA-7 (miR-7) plays an important role in the pathology of various diseases. However, the potential role of miR-7 in brain tissue inflammation (BTI) remains unclear. Methods: We detected the expression of miR-7 in LPS-induced murine BTI model and observed the possible effects of miR-7 deficiency on the pathology of BTI. To elucidate the mechanism, the target gene of miR-7 was screened out by Gene chip assay and its potential roles in BTI were evaluated by Western blot, immunofluorescence, and RNAi assay, respectively.Results: MiR-7 was upregulated in brain tissue in BTI mice and its deficiency could significantly aggravate the pathology of brain tissue. Moreover, RORα, a new target molecule of miR-7, was upregulated in brain tissue from miR-7 deficiency BTI mice. Of note, downregulation of RORα could remarkably exacerbate the pathology of brain tissue and elevate the transduction of NF-κB and ERK1/2 signaling pathways in brain tissue from miR-7 deficiency BTI mice. Furthermore, RORα and miR-7 were dominantly co-expressed in neurons of BTI mice. Finally, RORα synergized with miR-7 to control the inflammatory reaction of neuronal cells in response to LPS stimulation.Conclusions: MiR-7 expression is upregulated in BTI model. Moreover, miR-7 synergizes with its target gene RORα to control the inflammation reaction of neurons, thereby orchestrating the pathology of BTI.

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miR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic Cancer

Cited by 48 publications

References 36 publications

CDR1as/miR‑7/CKAP4 axis contributes to the pathogenesis of abdominal aortic aneurysm by regulating the proliferation and apoptosis of primary vascular smooth muscle cells

CDR1as/miR‑7/CKAP4 axis contributes to the pathogenesis of abdominal aortic aneurysm by regulating the proliferation and apoptosis of primary vascular smooth muscle cells

miR‑7/SP1/TP53BP1 axis may play a pivotal role in NSCLC radiosensitivity

MicroRNA-7, synergizes with RORα, negatively controls the pathology of brain tissue inflammation

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