A molecular expression signature distinguishing follicular lesions in thyroid carcinoma using preamplification RT-PCR in archival samples

Denning, K; Smyth, Paul; Cahill, Suzanne; Finn, Stephen P.; Conlon, E; Li, Jing‐Huan; Flavin, Richard; Aherne, Sinéad; Guenther, Simone M; Ferlinz, Astrid; O’Leary, John; Sheils, Orla

doi:10.1038/modpathol.3800943

Cited by 34 publications

(31 citation statements)

References 37 publications

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“…This is consistent with the studies by Cai et al (10) on pancreatic duct adenocarcinoma, and by Chang et al (11) on prostate cancer. However, the results are conflicting with studies in thyroid and breast cancer (8,9). This may be associated with the different origins of the tumors.…”

Section: Discussioncontrasting

confidence: 55%

“…As a member of the Ras-related small GTPase family, Rab23 has been studied in various types of tumor, and whether it has a negative or positive role in tumor progression is a controversial issue (6)(7)(8)(9). In recent years, tumor-promoting roles for Rab23 have been reported in several types of tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Wang et al (7) reported that Rab23 was overexpressed in human astrocytoma and promoted cell migration and invasion through the regulation of Rac1. However, Denning et al (8) demonstrated that Rab23 exhibited low expression and served an inhibitory role in thyroid cancer progression. Furthermore, Liu et al (9) reported that Rab23 expression could inhibit proliferation and promote apoptosis in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

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Rab23 promotes the cisplatin resistance of ovarian cancer via the Shh-Gli-ABCG2 signaling pathway

Zhang

Feng²,

Wang

et al. 2018

Oncol Lett

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Abstract.As a novel member of the Rab GTPase family, the role of Rab23 has been reported in multiple types of tumor. However, to the best of our knowledge, the role of Rab23 in ovarian cancer (OC) has not yet been reported. In the present study, immunohistochemistry analysis demonstrated that Rab23 was upregulated in OC tissue; survival analysis indicated that Rab23 expression was associated with a reduced overall survival (OS) rate and disease-free survival (DFS) time. In vitro experiments also demonstrated the increased expression of Rab23 in the OC cells lines, A2780 and SKOV-3, compared with in the normal ovarian cell line, IOSE80. Following the silencing of ABCG2 in SKOV-3 cells, ATP-binding cassette sub-family G member 2 (ABCG2) expression was significantly downregulated both at the RNA and protein levels. The cisplatin (DDP) IC 50 declined from 43.09±7.12 µmol/l in control cells to 26.46±5.38 µmol/l in SKOV-3 cells with silenced Rab23. In contrast, in A2780 cells overexpressing Rab23 (A2780-Rab23), ABCG2 expression was significantly upregulated and the DDP IC 50 increased from 27.42±6.54 µmol/l in control cells to 45.92±5.23 µmol/l in A2780-Rab23. Investigation into the potential molecular mechanisms for this revealed that the expression of sonic hedgehog (Shh) and Gli family zinc finger 1 (Gli1) was increased in A2780-Rab23 cells, whereas silencing Rab23 in SKOV-3 cells significantly inhibited the expression of Shh and Gli1. The Gli1 inhibitor GANT-61 significantly abrogated the increased ABCG2 expression in A2780-Rab23 cells. Furthermore, the DDP IC 50 in A2780-Rab23 cells decreased significantly following the silencing of ABCG2 expression; the IC 50 declined from 51.66±8.32 µmol/l in A2780-Rab23 cells to 25.61±6.17 µmol/l in A2780-Rab23 cells with silenced ABCG2. Collectively, the results indicate that Rab23 promotes the DDP resistance of OC cells via the Shh-Gli1-ABCG2 pathway, providing the proof of principle for the further investigation of drug resistance therapy targeting Rab23.

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rab23 promotes the cisplatin resistance of ovarian cancer via the Shh-Gli-ABCG2 signaling pathway

Zhang

Feng²,

Wang

et al. 2018

Oncol Lett

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“…In addition, high Rab23 expression levels in adult mouse brains hinted at a postnatal function beyond embryogenesis. Elevated Rab23 has been found in hepatocellular carcinomas (HCC) (Liu et al, 2007;Sun et al, 2012), lung cancer tissues (Huang et al, 2011) and atrophic gastritis with intestinal metaplasia (Kim et al, 2007), and it is also associated with diffuse-type gastric cancer (dGC) (Hou et al, 2008) and the follicular adenoma type of thyroid tumors (Denning et al, 2007). Besides tumorigenesis, Rab23 is also upregulated in kidney mesangial cells of focal segmental glomerulosclerosis (FSGS) mice (Huang et al, 2009;Shui et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

A novel role for Rab23 in the trafficking of Kif17 to the primary cilium

Lim

Tang

2015

Journal of Cell Science

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The small GTPase Rab23 is an antagonist of sonic hedgehog (Shh) signaling during mouse development. Given that modulation of Shh signaling depends on the normal functioning of the primary cilium, and overexpression of Evi5L, a putative Rab23 GTPase-activating protein (GAP), leads to reduced ciliogenesis, Rab23 could have a role at the primary cilium. Here, we found that wild-type Rab23 and the constitutively active Rab23 Q68L mutant were enriched at the primary cilium. Therefore, we tested the role of Rab23 in the ciliary targeting of known cargoes and found that ciliary localization of the kinesin-2 motor protein Kif17 was disrupted in Rab23-depleted cells. Co-immunoprecipitation and affinity-binding studies revealed that Rab23 exists in a complex with Kif17 and importin β2 (the putative Kif17 ciliary import carrier), implying that Kif17 needs to bind to regulatory proteins like Rab23 for its ciliary transport. Although a ciliary-cytoplasmic gradient of nuclear Ran is necessary to regulate the ciliary transport of Kif17, Rab23 and Ran appear to have differing roles in regulating the ciliary entry of Kif17. Our findings have uncovered a hitherto unknown effector of Rab23 and demonstrate how Rab23 could mediate the transport of Kif17 to the primary cilium.

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“…eIF6-(assay ID Hs00158272_m1), Dicer-1-(assay ID 00229023_m1) and Drosha (assay ID 00203008_m1)-specific TaqMan probes were available as Assays-on-Demand from Applied Biosystems. Assays were gene dose corrected using CDKN-1B as endogenous control as previously described, 23 and normalized to 22 cases of normal whole ovary.…”

Section: Relative Quantification By Real-time Rt-pcr Analysismentioning

confidence: 99%

Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients

et al. 2008

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MicroRNAs are a group of small non-coding RNAs approximately 22 nucleotides in length. Recent work has shown differential expression of mature microRNAs in human cancers. Production and function of microRNAs require coordinated processing by proteins of the microRNA machinery. Dicer and Drosha (RNase III endonucleases) are essential components of the microRNA machinery. Recently, the ribosome anti-association factor eIF6 has also been found to have a role in microRNA-mediated post-transcriptional silencing. We characterized the alterations in the expression of genes encoding proteins of microRNA machinery in ovarian serous carcinoma. Protein expression of eIF6 and Dicer was quantified in a tissue microarray of 66 ovarian serous carcinomas. Dicer, Drosha and eIF6 mRNA expression was analysed using quantitative reverse transcription-PCR on an independent set of 50 formalin-fixed, paraffin-embedded ovarian serous carcinoma samples. Expression profiles of eIF6 and Dicer were correlated with clinicopathological and patient survival data. We provide definitive evidence that eIF6 and Dicer are both upregulated in a significant proportion of ovarian serous carcinomas and are associated with specific clinicopathological features, most notably low eIF6 expression being associated with reduced disease-free survival. The status of eIF6 and proteins of the microRNA machinery may help predict toxicity and susceptibility to future interfering RNA-based therapy.

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A molecular expression signature distinguishing follicular lesions in thyroid carcinoma using preamplification RT-PCR in archival samples

Cited by 34 publications

References 37 publications

Rab23 promotes the cisplatin resistance of ovarian cancer via the Shh-Gli-ABCG2 signaling pathway

Rab23 promotes the cisplatin resistance of ovarian cancer via the Shh-Gli-ABCG2 signaling pathway

A novel role for Rab23 in the trafficking of Kif17 to the primary cilium

Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients

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