miR-483-5p determines mitochondrial fission and cisplatin sensitivity in tongue squamous cell carcinoma by targeting FIS1

Fan, ST; Chen, Weixiong; Lv, Xiaobin; Tang, Qiong‐Lan; Sun, Lijuan; Liu, Bodu; Zhong, Jianglong; Lin, Zhaoyu; Wang, Youyuan; Li, Qunxing; Yu, Xin; Zhang, Hanqing; Li, Yilin; Wen, Bin; Zhang, Zhang; Chen, Wei‐liang; Li, Jinsong

doi:10.1016/j.canlet.2015.03.045

Cited by 69 publications

(66 citation statements)

References 33 publications

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“…Therefore, our study could not exclude the role of miR-483-5p in the synovium in this process, which is a limitation of the present in vivo study. miR-483-5p is associated with several pathological conditions, including tumors such as tongue squamous cell carcinoma, 19 colorectal cancer, 20 and lung adenocarcinoma; 21 cartilage-associated pathologies such as osteoarthritis; 22,23 and bone-associated pathologies such as osteoporosis. Therefore, its targets refer to multiple pathways.…”

Section: Discussionmentioning

confidence: 99%

“…miR-483 is a multifunctional miRNA that regulates cell proliferation, differentiation, and migration in adipocytes, 16,17 pancreatic beta cells, 18 and various tumor cells. [19][20][21] Recently, miR-483-5p was reported to be upregulated in chondrocytes from OA patients, 22,23 as well as in cartilage from OA and old mice compared with their controls. 24 However, the functional role of miR-483-5p in OA development and the mechanisms through which miR-483-5p controls the fate of chondrocytes and regulates the pathogenesis of OA are not known.…”

Section: Introductionmentioning

confidence: 99%

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Intra-articular Delivery of Antago-miR-483-5p Inhibits Osteoarthritis by Modulating Matrilin 3 and Tissue Inhibitor of Metalloproteinase 2

et al. 2017

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MicroRNAs (miRNAs) are emerging as important regulators in osteoarthritis (OA) pathogenesis. In our study, a real-time PCR assay revealed that miR-483-5p was upregulated in articular cartilage from OA patients and experimental OA mice induced by destabilization of the medial meniscus compared to their controls. Overexpression of miR-483-5p by intra-articular injection of lentivirus LV3-miR-483-5p significantly enhanced the severity of experimental OA. Consequently, we synthesized antago-miR-483-5p to silence the endogenous miR-483-5p and delivered it intra-articularly, which revealed that antagomiR-483-5p delayed the progression of experimental OA. To investigate the functional mechanism of miR-483-5p in OA development, we generated doxycycline-inducible miR-483 transgenic (TG483) mice. TG483 mice exhibited significant acceleration and increased severity of OA, and age-related OA occurred with higher incidence and greater severity in TG483 mice compared with their controls. Furthermore, our results revealed miR-483-5p directly targeted to the cartilage matrix protein matrilin 3 (Matn3) and tissue inhibitor of metalloproteinase 2 (Timp2) to stimulate chondrocyte hypertrophy, extracellular matrix degradation, and cartilage angiogenesis, and it consequently initiated and accelerated the development of OA. In conclusion, our findings reveal an miRNA functional pathway important for OA development. Targeting of miR-483-5p by intra-articular injection of antago-miR-483-5p represents an approach that could prevent the onset of OA and delay its progression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intra-articular Delivery of Antago-miR-483-5p Inhibits Osteoarthritis by Modulating Matrilin 3 and Tissue Inhibitor of Metalloproteinase 2

et al. 2017

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“…The pro-apoptotic Fis1 activity, however, is likely independent from its fission activity, since it is conserved when mitochondrial morphology is corrected by manipulating Opa1 level (65). In adrenocortical cancer cells, the microRNA miR-484 suppresses Fis1 translation and inhibits apoptosis (68), while miR-483-5p targets Fis1, inhibits mitochondrial fission and cisplatin sensitivity in tongue squamous cell carcinoma (69). Overexpression of Fis1 (and of Drp1) has been observed in oncocytic thyroid tumors (70) and has been associated with poor prognosis in patients with acute myeloid leukemia (71).…”

Section: Deregulated Mitochondrial Dynamics In Cancer Cellsmentioning

confidence: 99%

The Concerted Action of Mitochondrial Dynamics and Positioning: New Characters in Cancer Onset and Progression

2017

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Mitochondria are dynamic organelles whose morphology and activity are extremely variable, depending on the metabolic state of the cell. In particular, their shape and movements within the cell are finely regulated by an increasing number of proteins, which take part in the process of mitochondrial fission/fusion and connect the organelles to the cytoskeleton. As to their activities, mitochondria are considered to be at the crossroad between cell life and death since, on the one hand, they are essential in ATP production and in multiple metabolic pathways but, on the other, they are involved in the intrinsic apoptotic cascade, triggered by different stress conditions. Importantly, the process of mitochondrial Ca2+ uptake, as well as the morphology and the dynamics of these organelles, is known to deeply impact on both pro-survival and pro-death mitochondrial activities. Recently, increasing evidence has accrued on a central role of deregulated mitochondrial functionalities in the onset and progression of different pathologies, ranging from neurodegenerative diseases to cancer. In this contribution, we will present the latest findings connecting alterations in the machineries that control mitochondrial dynamics and localization to specific cancer hallmarks, highlighting the importance of mitochondria for the viability of cancer cells and discussing their role as promising targets for the development of novel anticancer therapies.

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“…Several studies demonstrated that targeting DRP1 and mitochondrial fission may be an effective approach in cancer treatment [14]. Additionally, Fission, Mitochondrial 1 (FIS1), which serves as a receptor to recruit DRP1 to mitochondria, has also been uncovered to promote CDDP sensitivity in tongue squamous cell carcinoma [15]. This information suggests a close relationship between DRP1-mediated mitochondrial fission and CDDP sensitivity in cancer.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-148a-3p enhances cisplatin cytotoxicity in gastric cancer through mitochondrial fission induction and cyto-protective autophagy suppression

Wang

et al. 2017

Cancer Letters

112

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Cisplatin (CDDP) resistance is a major clinical problem associated with poor prognosis in gastric cancer (GC) patients. In this study, we performed integrated analysis of TCGA data from microRNAs (miRNAs) expression matrix of GC patients who received CDDP-based chemotherapy with GEO dataset which contains differential miRNAs expression profiles in CDDP-resistant and -sensitive cell lines. We identified miR-148a-3p downregulation as a key step involved in CDDP resistance. Using a cohort consisting 105 GC patients who received CDDP-based therapy, we found that miR-148a-3p downregulation was associated with a decrease in patients’ disease-free survival (DFS, P=0.0077). A series of experiment data demonstrated that: 1) miR-148a-3p was downregulated in CDDP-resistant GC cell lines; 2) miR-148a-3p reconstitution sensitized CDDP-resistant cells to CDDP treatment through promoting mitochondrial fission and decreasing AKAP1 expression level; 3) AKAP1 played a novel role in CDDP resistance by inhibiting P53-mediated DRP1 dephosphorylation; 4) miR-148a-3p reconstitution in CDDP-resistant cells inhibits the cyto-protective autophagy by suppressing RAB12 expression and mTOR1 activation. Taken together, our study demonstrates that miR-148a-3p could be a promising prognostic marker or therapeutic candidate for overcoming CDDP resistance in GC.

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miR-483-5p determines mitochondrial fission and cisplatin sensitivity in tongue squamous cell carcinoma by targeting FIS1

Cited by 69 publications

References 33 publications

Intra-articular Delivery of Antago-miR-483-5p Inhibits Osteoarthritis by Modulating Matrilin 3 and Tissue Inhibitor of Metalloproteinase 2

Intra-articular Delivery of Antago-miR-483-5p Inhibits Osteoarthritis by Modulating Matrilin 3 and Tissue Inhibitor of Metalloproteinase 2

The Concerted Action of Mitochondrial Dynamics and Positioning: New Characters in Cancer Onset and Progression

MicroRNA-148a-3p enhances cisplatin cytotoxicity in gastric cancer through mitochondrial fission induction and cyto-protective autophagy suppression

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