MiR-887 Promotes the Progression of Hepatocellular Carcinoma via Targeting VHL

Zou, Wei; Cheng, Jun

doi:10.1177/1533033820940425

Cited by 4 publications

(5 citation statements)

References 28 publications

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“…There are many miRNAs that have been implicated in CRC carcinogenesis and progression. The miRNA, miR-887-3p, contains 22 bases localized at the chromosomal locus 5q15.1 and has been reportedly involved in the progression of pancreatic cancer [ 10 ], hepatocellular carcinoma [ 11 ], and breast cancer [ 12 ]. However, the biological role and detailed mechanism of miR-887-3p in CRC remain to be further investigated, which could prove a novel molecule with regulatory function on CRC.…”

Section: Introductionmentioning

confidence: 99%

miR-887-3p Inhibits the Progression of Colorectal Cancer via Downregulating DNMT1 Expression and Regulating P53 Expression

Teng

Xia

et al. 2022

Computational Intelligence and Neuroscience

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Colorectal cancer (CRC) is the third most diagnosed cancer worldwide and the second leading cause of cancer-related deaths. Many researchers have reported that abnormal microRNAs (miRs) were expressed in CRC and participated in the occurrence and progression of CRC. However, there are few reports of miR-887-3p regulating CRC development. In the current study, we investigated the abnormal expression of miR-887-3p and also demonstrated its regulatory role and detailed molecular mechanism in CRC. Initially, miRNA expression data were obtained from TCGA-COAD that consisted of 453 CRC samples and 8 normal tissue samples. These were downloaded and analyzed to compare the expression level of miR-887-3p in CRC tissues to that in normal tissues. Moreover, 32 pairs of surgically resected CRC tumors and para-cancer tissues from our hospital were collected. Quantitative real-time PCR (qRT-PCR) was performed to detect miR-887-3p expression levels in CRC tissues, para-cancer tissues, several CRC cell lines, and an intestinal epithelial cell line. Following miR-887-3p mimic transfection in colon cancer SW480 cell line, the regulatory roles of miR-887-3p on cell proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT) were detected through CCK-8, flow cytometry, transwell assay, and Western blot. After potential targeting protein was predicted by bioinformatic websites, the luciferase reporter assay and Western blot were used to confirm the target of miR-887-3p. The targeting protein expressions were detected by Western blot and qRT-PCR. The relationship between miR-887-3p level and the effect of miR-887-3p on P53 expression was evaluated by Western blot and qRT-PCR. The effects of miR-887-3p on CRC cell growth in vivo by xenograft tumor experiments were investigated, and Ki-67 in tumor tissue was determined by immunohistochemistry. Results. The COAD data demonstrated that the expression levels of miR-887-3p in CRC clinical sample tissues and cell line cultures were remarkably lower than para-cancer normal tissues and NCM460 cells (normal colonic epithelial cell line). Functional experiments demonstrated that overexpression of miR-887-3p in SW480 cells significantly reduced proliferation, migration, invasion, and EMT, and promoted cancer cell apoptosis. Additionally, Western blot, qRT-PCR, and luciferase reporter assays confirmed that DNMT1 was a downstream target of miR-887-3p. Moreover, the blocking of DNMT1 by miR-887-3p mimics also promoted P53 expression. Finally, overexpression of DNMT1 in SW480 cells could partially reverse the regulatory effect of miR-887-3p mimics on CRC cell development. From in vivo experiments, overexpression of miR-887-3p could inhibit tumor growth in CRC xenograft mice and reduce the Ki-67 level. Conclusion. The microRNA miR-887-3p is a potential biomarker of CRC. It inhibited CRC cell proliferation, invasion, and EMT, and promoted cell apoptosis through targeting and downregulating DNMT1 and promoting P53 expression. Therefore, miR-887-3p may be a good biomarker and therapeutic target for CRC treatment.

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Section: Introductionmentioning

confidence: 99%

miR-887-3p Inhibits the Progression of Colorectal Cancer via Downregulating DNMT1 Expression and Regulating P53 Expression

Teng

Xia

et al. 2022

Computational Intelligence and Neuroscience

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“…In addition, miRNAs may target signaling molecules such as HIF-1 that promote metabolic adaptation in tumor cells [ 23 ]. In addition, miRNAs have been reported to target HIF1A , VHL , CUL , RBX1 , and ELOC [ 24 , 25 , 26 ]. Additionally, the E6 and E7 oncoproteins of HPV 16 lead to aberrant miRNA expression; a large number of these miRNA genes are downstream mRNA targets essential in normal cell maintenance [ 22 , 60 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, miRNAs may target signaling molecules such as HIF-1 that facilitate metabolic adaptation in tumor cells [ 23 ]. Interestingly, some miRNAs have been reported to target HIF1A , VHL , CUL , RBX1 , and ELOC [ 24 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Bioinformatics Analysis Reveals E6 and E7 of HPV 16 Regulate Metabolic Reprogramming in Cervical Cancer, Head and Neck Cancer, and Colorectal Cancer through the PHD2-VHL-CUL2-ELOC-HIF-1α Axis

Arizmendi-Izazaga,

Navarro-Tito,

Jiménez-Wences

et al. 2024

CIMB

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Human papillomavirus 16 (HPV 16) infection is associated with several types of cancer, such as head and neck, cervical, anal, and penile cancer. Its oncogenic potential is due to the ability of the E6 and E7 oncoproteins to promote alterations associated with cell transformation. HPV 16 E6 and E7 oncoproteins increase metabolic reprogramming, one of the hallmarks of cancer, by increasing the stability of hypoxia-induced factor 1 α (HIF-1α) and consequently increasing the expression levels of their target genes. In this report, by bioinformatic analysis, we show the possible effect of HPV 16 oncoproteins E6 and E7 on metabolic reprogramming in cancer through the E6-E7-PHD2-VHL-CUL2-ELOC-HIF-1α axis. We proposed that E6 and E7 interact with VHL, CUL2, and ELOC in forming the E3 ubiquitin ligase complex that ubiquitinates HIF-1α for degradation via the proteasome. Based on the information found in the databases, it is proposed that E6 interacts with VHL by blocking its interaction with HIF-1α. On the other hand, E7 interacts with CUL2 and ELOC, preventing their binding to VHL and RBX1, respectively. Consequently, HIF-1α is stabilized and binds with HIF-1β to form the active HIF1 complex that binds to hypoxia response elements (HREs), allowing the expression of genes related to energy metabolism. In addition, we suggest an effect of E6 and E7 at the level of PHD2, VHL, CUL2, and ELOC gene expression. Here, we propose some miRNAs targeting PHD2, VHL, CUL2, and ELOC mRNAs. The effect of E6 and E7 may be the non-hydroxylation and non-ubiquitination of HIF-1α, which may regulate metabolic processes involved in metabolic reprogramming in cancer upon stabilization, non-degradation, and translocation to the nucleus.

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“…Transcritional regulation of ALDH2 through interaction with its transcription factor HNF-4α NDRG3, N-Myc downstream-regulated gene 3; NF-κB, nuclear factor-κB; HIF, hypoxia-inducible factor; HuR, human antigen R (also known as ELAV1); NGF, nerve growth factor; RB, retinoblastoma protein;CARD9, Caspase Recruitment Domain Family Member 9; CK2, Casein kinase II; RAPTOR, regulatory-associated protein of the mechanistic target of rapamycin complex 1 (mTORC1); ALDH2, aldehyde dehydrogenase 2; HNF-4α, hepatocyte nuclear factor 4 alpha. miR-21 hepatic stellate cells; papillary thyroid carcinoma; pancreatic carcinoma; cervical carcinoma cells [122]; [86]; [123]; [124] miR-23b glioma cells [125] miR-92 epithelial ovarian carcinoma; clear cell renal cell carcinoma [116]; [117] miR-101 breast carcinoma cells [126] miR-150 glioma cells [127] miR-155 breast carcinoma cells [78] miR-222 retinoblastoma cells [128] miR-224 renal cell carcinoma cells [121] miR-331-3p hepatocellular carcinoma cells [129] miR-429 HER2+ breast carcinoma cells [130] miR-566 glioblastoma cells [131] miR-887 hepatocellular carcinoma cells [132]…”

Section: Discussionmentioning

confidence: 99%

VHL tumor suppressor as a novel potential candidate biomarker in papillary thyroid carcinoma

Todorović

Stanojević

2022

Bosn J of Basic Med Sci

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Papillary thyroid carcinoma (PTC) is the most common type of endocrine cancer, with an increasing incidence worldwide. The treatment of PTC is currently the subject of clinical controversy, making it critically important to identify molecular markers that would help improve the risk stratification of PTC patients and optimize the therapeutic approach. The VHL tumor suppressor gene has been implicated in tumorigenesis of various types of carcinoma and linked with their aggressive biological behavior. The role of VHL in the origin and development of PTC has only recently begun to be revealed. In this narrative review we attempt to summarize the existing knowledge that implicates VHL in PTC pathogenesis and to outline its potential significance as a candidate molecular biomarker for the grouping of PTC patients into high and low risk groups.

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MiR-887 Promotes the Progression of Hepatocellular Carcinoma via Targeting VHL

Cited by 4 publications

References 28 publications

miR-887-3p Inhibits the Progression of Colorectal Cancer via Downregulating DNMT1 Expression and Regulating P53 Expression

miR-887-3p Inhibits the Progression of Colorectal Cancer via Downregulating DNMT1 Expression and Regulating P53 Expression

Bioinformatics Analysis Reveals E6 and E7 of HPV 16 Regulate Metabolic Reprogramming in Cervical Cancer, Head and Neck Cancer, and Colorectal Cancer through the PHD2-VHL-CUL2-ELOC-HIF-1α Axis

VHL tumor suppressor as a novel potential candidate biomarker in papillary thyroid carcinoma

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