PIWI‐interacting RNA 39980 promotes tumor progression and reduces drug sensitivity in neuroblastoma cells

Roy, Jyoti; Das, Basudeb; Jain, Neha; Mallick, Bibekanand

doi:10.1002/jcp.29136

Cited by 29 publications

(26 citation statements)

References 63 publications

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“…Neither piR‐FTH1 nor piR‐932 was present in our samples. A few other studies have also reported functional mechanisms of piRNAs in cancer but they lack validation of the interaction with PIWI‐proteins and two of the reported piRNAs align with snoRNAs 47‐51 . Although these findings shed light on the possible functional roles of individual piRNAs in cancer, whether and how the majority of the observed dysregulated piRNAs in cancer affect tumorigenesis remain unknown.…”

Section: Discussionmentioning

confidence: 90%

The debatable presence of PIWI‐interacting RNAs in invasive breast cancer

et al. 2021

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Numerous factors influence breast cancer (BC) prognosis, thus complicating the prediction of outcome. By identifying biomarkers that would distinguish the cases with poorer response to therapy already at the time of diagnosis, the rate of survival could be improved. Lately, Piwi‐interacting RNAs (piRNAs) have been introduced as potential cancer biomarkers, however, due to the recently raised challenges in piRNA annotations, further evaluation of piRNAs’ involvement in cancer is required. We performed small RNA sequencing in 227 fresh‐frozen breast tissue samples from the Eastern Finnish Kuopio Breast Cancer Project material to study the presence of piRNAs in BC and their associations with the clinicopathological features and outcome of BC patients. We observed the presence of three small RNAs annotated as piRNA database entries (DQ596932, DQ570994, and DQ571955) in our samples. The actual species of these RNAs however remain uncertain. All three small RNAs were upregulated in grade III tumors and DQ596932 additionally in estrogen receptor negative tumors. Furthermore, patients with estrogen receptor positive BC and higher DQ571955 had shorter relapse‐free survival and poorer BC‐specific survival, thus indicating DQ571955 as a candidate predictive marker for radiotherapy response in estrogen receptor positive BC. DQ596932 showed possible prognostic value in BC, whereas DQ570994 was identified as a candidate predictive marker for tamoxifen and chemotherapy response. These three small RNAs appear as candidate biomarkers for BC, which could after further investigation provide novel approaches for the treatment of therapy resistant BC. Overall, our results indicate that the prevalence of piRNAs in cancer is most likely not as comprehensive as has been previously thought.

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Section: Discussionmentioning

confidence: 90%

The debatable presence of PIWI‐interacting RNAs in invasive breast cancer

et al. 2021

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“…OS cells were seeded at a density of 2 × 10 5 cells/well and transfected with 80 nM mimic/scramble/inhibitor/NC. After 24 h of transfection, nuclear accumulation of phosphorylated histone H2AX (γ‐H2AX) in OS cells was detected by performing immunofluorescence microscopy of γ‐H2AX as reported in our previous study [Roy et al., ]. Rabbit anti‐γ‐H2AX (phosphor S139) antibody (ab81299, Abcam) and DyLight‐488 conjugated secondary antibody (ab96899, Abcam) were used in this study.…”

Section: Methodsmentioning

confidence: 99%

piR‐39980 promotes cell proliferation, migration and invasion, and inhibits apoptosis via repression of SERPINB1 in human osteosarcoma

Das

Jain

Mallick

2020

Biology of the Cell

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Background Information Piwi‐interacting RNAs (piRNAs) are a novel class of ∼23–36 nts long endogenous small non‐coding RNAs, earlier known to maintain germline genome integrity during development by regulating transposable elements. Recently, piRNAs are known to regulate cell proliferation, apoptosis and metastasis in different cancer cells. However, piRNAs have not yet been reported in human osteosarcoma (OS), a highly metastatic aggressive bone tumour among adolescents. Therefore, our current study aimed to decrypt the potential role of a piRNA, piR‐39980 in osteosarcoma, which was earlier reported by us in fibrosarcoma, neuroblastoma and epithelial ovarian cancer. Results We found that piR‐39980 is significantly upregulated in two human osteosarcoma cell lines, 143B and HOS compared to IMR90‐tert fibroblast cells. The transient overexpression of endogenous piR‐39980 level through transfection by piRNA mimic promotes proliferation, migration and invasion ability of OS cells, whereas its inhibition significantly induces apoptosis, chromatin condensation and γ‐H2AX accumulation as well as restrains migration and invasion of OS cells. Further, we found 13 genes as targets of piR‐39980 using miRanda, among which SERPINB1 that is downregulated in OS cells is seen to suppress proliferation, and migration in this cancer upon its overexpression. The knockdown of piR‐39980 in OS cells led to enhanced expression of SERPINB1 indicating to be its target, which was then confirmed by dual luciferase reporter assay. In addition, gelatin zymography and western blotting revealed that transfection of piR‐39980 mimic promotes MMP‐2 activation, whereas its inhibition and SERPINB1 overexpression suppresses MMP‐2 activation in OS cells. Conclusions Taken together, our study revealed that piR‐39980 promotes migration and invasion via MMP‐2 activation as well as inhibits cell death, both through negative regulation of SERPINB1. Significance This study revealed that piR‐39980 functions as an oncogene in human osteosarcoma, which could be harnessed as a potential therapeutic target for this malignancy.

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“…Cell viability and proliferation were measured by MTT {3‐(4,5‐dimethylthiazol‐2yl)−2,5‐diphenyltetrazolium bromide} reduction assay according to our previous method . Briefly, 5 × 10 3 HT1080 cells per 100 μL of culture media were seeded in triplicate in a 96‐well plate.…”

Section: Methodsmentioning

confidence: 99%

“…Cell viability and proliferation were measured by MTT {3-(4,5-dimethylthiazol-2yl)−2,5-diphenyltetrazolium bro-mide} reduction assay according to our previous method. 24 Briefly, 5 × 10 3 HT1080 cells per 100 μL of culture media were seeded in triplicate in a 96-well plate. When cells reach confluency, they were transfected with miR-197-3p mimic and scramble in a concentration-dependent manner (20,40,60,80, and 100 nM).…”

Section: Cell Viability Assaymentioning

confidence: 99%

Restoration of microRNA‐197 expression suppresses oncogenicity in fibrosarcoma through negative regulation of RAN

2020

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MicroRNAs (miRNAs) act as crucial regulators of biological pathways/processes by reinforcing transcriptional programs and moderating transcripts. Emerging evidences have shown the involvement of dysregulated miRNAs in pathophysiology of human diseases including several cancer types. Recently, miR‐197‐3p has been reported to play different roles in different cancers; however, its role in fibrosarcoma, a highly aggressive and malignant soft tissue sarcoma originated from the mesenchymal tissues, has not yet been studied. Therefore, this study aims to investigate the possible regulatory roles of miR‐197‐3p in the oncogenicity of fibrosarcoma. For this, we initially performed qRT‐PCR of miR‐197‐3p, which we found to be downregulated in HT1080 human fibrosarcoma cells compared with IMR90‐tert normal fibroblast cells. Subsequently, we performed gain‐of‐function study by employing several methods such as MTT assay, clonogenic assay, wound healing, flow cytometry cell cycle analysis, and acridine orange staining after transfecting HT1080 cells with miR‐197‐3p mimic. From these assays, we observed that miR‐197‐3p significantly inhibits viability, colony forming, and migration ability as well as triggers G2/M phase cell cycle arrest and autophagy in fibrosarcoma cells. To understand the mechanism through which miRNA performs these functions, we predicted its targets using TargetScan and performed pathway enrichment analysis after screening them by their expression in fibrosarcoma. Among the enriched targets, we found RAN (ras‐related nuclear protein) to be a crucial target through which miR‐197‐3p represses tumorigenesis by binding to its 3´ UTR, validated by luciferase reporter assay. The tumor suppressive role of the miRNA was further confirmed by transfecting its mimic in RAN‐overexpressed cells which showed significant attenuation in tumorigenic effect of RAN in fibrosarcoma as seen in different assays. Taken together, our study unveiled that miR‐197‐3p acts as an oncosuppressor in fibrosarcoma through G2/M phase arrest and induction of autophagy, and raises the possibility to act as a novel therapeutic intervention for the malignancy.

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PIWI‐interacting RNA 39980 promotes tumor progression and reduces drug sensitivity in neuroblastoma cells

Cited by 29 publications

References 63 publications

The debatable presence of PIWI‐interacting RNAs in invasive breast cancer

The debatable presence of PIWI‐interacting RNAs in invasive breast cancer

piR‐39980 promotes cell proliferation, migration and invasion, and inhibits apoptosis via repression of SERPINB1 in human osteosarcoma

Restoration of microRNA‐197 expression suppresses oncogenicity in fibrosarcoma through negative regulation of RAN

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