Loss of MiR-664 Expression Enhances Cutaneous Malignant Melanoma Proliferation by Upregulating PLP2

Ding, Zhenhua; Sun, Jian; Peng, Xuebiao; Liu, Yimin; Wang, Yunlong; Li, Zheng; Ou, Chengshan; Wang, Yinghui; Zeng, Weixia; Zhou, Meijuan

doi:10.1097/md.0000000000001327

Cited by 36 publications

(41 citation statements)

References 51 publications

(38 reference statements)

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“…PLP2 had been shown to involve in various cancers, including breast cancer, hepatocellular carcinoma, osteosarcoma, and melanoma. 13 Zhu et al reported that miR-664 directly targeted the 3 0 UTR region of PLP2 in T-cell acute lymphoblastic leukemia. 19 Ding et al suggested that PLP2 was a bona fide target of miR-664 in cutaneous malignant melanoma.…”

Section: Discussionmentioning

confidence: 99%

“…Proteolipid protein 2 (PLP2), also known as A4 protein, has been shown to be upregulated in several cancers, including melanoma cancer, alzheimer's disease, renal cell carcinoma and so on. 13,14 Its overexpression enhances cell proliferation, adhesion, and invasion in melanoma cells. 13 It is also involved in CCR1 signaling pathway and stimulates the migration of human osteosarcoma cells.…”

Section: Introductionmentioning

confidence: 99%

“…13,14 Its overexpression enhances cell proliferation, adhesion, and invasion in melanoma cells. 13 It is also involved in CCR1 signaling pathway and stimulates the migration of human osteosarcoma cells. 15 However, except from the study of Longo A et.al, no correlation between PLP2 and breast cancer cells have been reported before.…”

Section: Introductionmentioning

confidence: 99%

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MiR-422a weakened breast cancer stem cells properties by targeting PLP2

Zou

Chen

Yao

et al. 2018

Cancer Biology & Therapy

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MiR-422a weakened breast cancer stem cells properties by targeting PLP2

Zou

Chen

Yao

et al. 2018

Cancer Biology & Therapy

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“…miR-664b-5p was also recently shown to act as a cancer suppressor in hepatocellular cancer cell lines 96 . The downregulated miR-664b-5p was associated with lower overall survival in cervical cancer 97 , the proliferation of cutaneous malignant melanoma cells 98 , and the progression of breast cancer 99 . The role of the miRNA is associated with the downregulation of AKT2 96 .…”

Section: Hsa-mir-664bmentioning

confidence: 96%

Pan-Cancer analysis of somatic mutations in miRNA genes

Urbanek-Trzeciak

Galka-Marciniak

Nawrocka

et al. 2020

Preprint

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175)miRNAs are considered important players in oncogenesis, serving either as oncomiRs or suppressormiRs. Although the accumulation of somatic alterations is an intrinsic aspect of cancer development and many important cancer-driving mutations have been identified in protein-coding genes, the area of functional somatic mutations in miRNA genes is heavily understudied. Here, based on analysis of the whole-exome sequencing of over 10,000 cancer/normal sample pairs deposited within the TCGA repository, we identified and characterized over 10,000 somatic mutations in miRNA genes and showed that some of the genes are overmutated in Pan-Cancer and/or specific cancers. Nonrandom occurrence of the identified mutations was confirmed by a strong association of overmutated miRNA genes with KEGG pathways, most of which were related to specific cancer types or cancer-related processes. Additionally, we showed that mutations in some of the overmutated genes correlate with miRNA expression, cancer staging, and patient survival. Our results may also be the first step (form the basis and provide the resources) in the development of computational and/or statistical approaches/tools dedicated to the identification of cancerdriver miRNA genes. The results published here are based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga. This work was supported by research grants from the Polish National Science Centre [2016/22/A/NZ2/00184 (to P.K.) and 2015/17/N/NZ3/03629 (to M.O.U-T.)] Authors contributions MUTparticipated in conceiving the study, wrote all the scripts, performed most of the computational and statistical analyses, drafted the manuscript, prepared figures, tables, and supplementary materials; PGMparticipated in conceiving the study, discussed the study on all steps of analyses, participated in manuscript preparation, performed some analyses (3D structures); PNdiscussed the analyses on all steps of the study, performed some analyses, participated in manuscript preparation; EKperformed the sequencing experiments, critically read and corrected manuscript; SSperformed the sequencing experiments, critically read and corrected manuscript; MGprovided samples for the hsa-miR-1324 and hsa-miR-142 sequencing validation experiments, advised on hematological neoplasms and head and neck cancer, critically read and corrected manuscript; PKreceived financing, participated in conceiving the study, supervised and coordinated the study, drafted the manuscript (with MUT).

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“…Several reports have shown that PLP2 is highly expressed in extracranial cancers where it has been shown to promote tumour growth and metastasis. 4,22,23 To assess the biological role of PLP2 in glioma, we knocked down PLP2 expression in U87 and U251 GBM cells, using two small interfering RNAs (siPLP2-1 and siPLP2-2). Significant knockdown of PLP2 expression levels was obtained (Figure 2A and Figure S2A).…”

Section: Down-regulation Of Plp2 Inhibits Cell Proliferation In Glimentioning

confidence: 99%

Reduced expression of proteolipid protein 2 increases ER stress‐induced apoptosis and autophagy in glioblastoma

Feng

Wang

et al. 2019

J Cellular Molecular Medi

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Proteolipid protein 2 (PLP2) is an integral ion channel membrane protein of the endoplasmic reticulum. The protein has been shown to be highly expressed in many cancer types, but its importance in glioma progression is poorly understood. Using publicly available datasets (Rembrandt, TCGA and CGGA), we found that the expression of PLP2 was significantly higher in high‐grade gliomas than in low‐grade gliomas. We confirmed these results at the protein level through IHC staining of high‐grade (n = 56) and low‐grade glioma biopsies (n = 16). Kaplan‐Meier analysis demonstrated that increased PLP2 expression was associated with poorer patient survival. In functional experiments, siRNA and shRNA PLP2 knockdown induced ER stress and increased apoptosis and autophagy in U87 and U251 glioma cell lines. Inhibition of autophagy with chloroquine augmented apoptotic cell death in U87‐ and U251‐siPLP2 cells. Finally, intracranial xenografts derived from U87‐ and U251‐shPLP2 cells revealed that loss of PLP2 reduced glioma growth in vivo. Our results therefore indicate that increased PLP2 expression promotes GBM growth and that PLP2 represents a potential future therapeutic target.

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Loss of MiR-664 Expression Enhances Cutaneous Malignant Melanoma Proliferation by Upregulating PLP2

Abstract: Supplemental Digital Content is available in the text

Cited by 36 publications

References 51 publications

MiR-422a weakened breast cancer stem cells properties by targeting PLP2

MiR-422a weakened breast cancer stem cells properties by targeting PLP2

Pan-Cancer analysis of somatic mutations in miRNA genes

Reduced expression of proteolipid protein 2 increases ER stress‐induced apoptosis and autophagy in glioblastoma

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