1.Differential expression of ORAI channels and STIM proteins in renal cell carcinoma subtypes: implications for metastasis and therapeutic targeting
Ji-Hee KIM ; Kyu-Hee HWANG ; Jiyeon OH ; Sung-Eun KIM ; Mi-Young LEE ; Tae Sic LEE ; Seung-Kuy CHA
The Korean Journal of Physiology and Pharmacology 2025;29(1):33-43
Renal cell carcinoma (RCC) presents significant clinical challenges, highlighting the importance of understanding its molecular mechanisms. While store-operated Ca2+ entry (SOCE) is known to play an essential role in tumorigenesis and metastasis, its specific implications across various RCC subtypes remain underexplored.This study analyzed SOCE-related mRNA profiles from the KIRC and KIRP projects in The Cancer Genome Atlas (TCGA) database, focusing on differential gene expression and overall survival outcomes. Functional studies in clear cell RCC (Caki-1) and papillary RCC cell lines (pRCC, Caki-2) revealed increased expression of Orai1 and Orai3, along with STIM1, exhibited in both subtypes, with decreased STIM2 and increased Orai2 expression in pRCC. Notably, Orai3 expression had a gender-specific impact on survival, particularly in females with pRCC, where it inversely correlated with STIM2 expression. Functional assays showed Orai3 dominance in Caki-2 and Orai1 in Caki-1. Interestingly, 2-APB inhibited SOCE in Caki-1 but enhanced it in Caki-2, suggesting Orai3 as the primary SOCE channel in pRCC. Knockdown of Orai1 and Orai3 reduced cell migration and proliferation via regulating focal adhesion kinase (FAK) and Cyclin D1 in both cell lines. These findings highlight the critical roles of Orai1 and Orai3 in RCC metastasis, with Orai3 linked to poorer prognosis in females with pRCC. This study offers valuable insights into RCC diagnostics and potential therapeutic strategies targeting ORAI channels and STIM proteins.
2.Differential expression of ORAI channels and STIM proteins in renal cell carcinoma subtypes: implications for metastasis and therapeutic targeting
Ji-Hee KIM ; Kyu-Hee HWANG ; Jiyeon OH ; Sung-Eun KIM ; Mi-Young LEE ; Tae Sic LEE ; Seung-Kuy CHA
The Korean Journal of Physiology and Pharmacology 2025;29(1):33-43
Renal cell carcinoma (RCC) presents significant clinical challenges, highlighting the importance of understanding its molecular mechanisms. While store-operated Ca2+ entry (SOCE) is known to play an essential role in tumorigenesis and metastasis, its specific implications across various RCC subtypes remain underexplored.This study analyzed SOCE-related mRNA profiles from the KIRC and KIRP projects in The Cancer Genome Atlas (TCGA) database, focusing on differential gene expression and overall survival outcomes. Functional studies in clear cell RCC (Caki-1) and papillary RCC cell lines (pRCC, Caki-2) revealed increased expression of Orai1 and Orai3, along with STIM1, exhibited in both subtypes, with decreased STIM2 and increased Orai2 expression in pRCC. Notably, Orai3 expression had a gender-specific impact on survival, particularly in females with pRCC, where it inversely correlated with STIM2 expression. Functional assays showed Orai3 dominance in Caki-2 and Orai1 in Caki-1. Interestingly, 2-APB inhibited SOCE in Caki-1 but enhanced it in Caki-2, suggesting Orai3 as the primary SOCE channel in pRCC. Knockdown of Orai1 and Orai3 reduced cell migration and proliferation via regulating focal adhesion kinase (FAK) and Cyclin D1 in both cell lines. These findings highlight the critical roles of Orai1 and Orai3 in RCC metastasis, with Orai3 linked to poorer prognosis in females with pRCC. This study offers valuable insights into RCC diagnostics and potential therapeutic strategies targeting ORAI channels and STIM proteins.
3.Differential expression of ORAI channels and STIM proteins in renal cell carcinoma subtypes: implications for metastasis and therapeutic targeting
Ji-Hee KIM ; Kyu-Hee HWANG ; Jiyeon OH ; Sung-Eun KIM ; Mi-Young LEE ; Tae Sic LEE ; Seung-Kuy CHA
The Korean Journal of Physiology and Pharmacology 2025;29(1):33-43
Renal cell carcinoma (RCC) presents significant clinical challenges, highlighting the importance of understanding its molecular mechanisms. While store-operated Ca2+ entry (SOCE) is known to play an essential role in tumorigenesis and metastasis, its specific implications across various RCC subtypes remain underexplored.This study analyzed SOCE-related mRNA profiles from the KIRC and KIRP projects in The Cancer Genome Atlas (TCGA) database, focusing on differential gene expression and overall survival outcomes. Functional studies in clear cell RCC (Caki-1) and papillary RCC cell lines (pRCC, Caki-2) revealed increased expression of Orai1 and Orai3, along with STIM1, exhibited in both subtypes, with decreased STIM2 and increased Orai2 expression in pRCC. Notably, Orai3 expression had a gender-specific impact on survival, particularly in females with pRCC, where it inversely correlated with STIM2 expression. Functional assays showed Orai3 dominance in Caki-2 and Orai1 in Caki-1. Interestingly, 2-APB inhibited SOCE in Caki-1 but enhanced it in Caki-2, suggesting Orai3 as the primary SOCE channel in pRCC. Knockdown of Orai1 and Orai3 reduced cell migration and proliferation via regulating focal adhesion kinase (FAK) and Cyclin D1 in both cell lines. These findings highlight the critical roles of Orai1 and Orai3 in RCC metastasis, with Orai3 linked to poorer prognosis in females with pRCC. This study offers valuable insights into RCC diagnostics and potential therapeutic strategies targeting ORAI channels and STIM proteins.
4.Differential expression of ORAI channels and STIM proteins in renal cell carcinoma subtypes: implications for metastasis and therapeutic targeting
Ji-Hee KIM ; Kyu-Hee HWANG ; Jiyeon OH ; Sung-Eun KIM ; Mi-Young LEE ; Tae Sic LEE ; Seung-Kuy CHA
The Korean Journal of Physiology and Pharmacology 2025;29(1):33-43
Renal cell carcinoma (RCC) presents significant clinical challenges, highlighting the importance of understanding its molecular mechanisms. While store-operated Ca2+ entry (SOCE) is known to play an essential role in tumorigenesis and metastasis, its specific implications across various RCC subtypes remain underexplored.This study analyzed SOCE-related mRNA profiles from the KIRC and KIRP projects in The Cancer Genome Atlas (TCGA) database, focusing on differential gene expression and overall survival outcomes. Functional studies in clear cell RCC (Caki-1) and papillary RCC cell lines (pRCC, Caki-2) revealed increased expression of Orai1 and Orai3, along with STIM1, exhibited in both subtypes, with decreased STIM2 and increased Orai2 expression in pRCC. Notably, Orai3 expression had a gender-specific impact on survival, particularly in females with pRCC, where it inversely correlated with STIM2 expression. Functional assays showed Orai3 dominance in Caki-2 and Orai1 in Caki-1. Interestingly, 2-APB inhibited SOCE in Caki-1 but enhanced it in Caki-2, suggesting Orai3 as the primary SOCE channel in pRCC. Knockdown of Orai1 and Orai3 reduced cell migration and proliferation via regulating focal adhesion kinase (FAK) and Cyclin D1 in both cell lines. These findings highlight the critical roles of Orai1 and Orai3 in RCC metastasis, with Orai3 linked to poorer prognosis in females with pRCC. This study offers valuable insights into RCC diagnostics and potential therapeutic strategies targeting ORAI channels and STIM proteins.
5.Differential expression of ORAI channels and STIM proteins in renal cell carcinoma subtypes: implications for metastasis and therapeutic targeting
Ji-Hee KIM ; Kyu-Hee HWANG ; Jiyeon OH ; Sung-Eun KIM ; Mi-Young LEE ; Tae Sic LEE ; Seung-Kuy CHA
The Korean Journal of Physiology and Pharmacology 2025;29(1):33-43
Renal cell carcinoma (RCC) presents significant clinical challenges, highlighting the importance of understanding its molecular mechanisms. While store-operated Ca2+ entry (SOCE) is known to play an essential role in tumorigenesis and metastasis, its specific implications across various RCC subtypes remain underexplored.This study analyzed SOCE-related mRNA profiles from the KIRC and KIRP projects in The Cancer Genome Atlas (TCGA) database, focusing on differential gene expression and overall survival outcomes. Functional studies in clear cell RCC (Caki-1) and papillary RCC cell lines (pRCC, Caki-2) revealed increased expression of Orai1 and Orai3, along with STIM1, exhibited in both subtypes, with decreased STIM2 and increased Orai2 expression in pRCC. Notably, Orai3 expression had a gender-specific impact on survival, particularly in females with pRCC, where it inversely correlated with STIM2 expression. Functional assays showed Orai3 dominance in Caki-2 and Orai1 in Caki-1. Interestingly, 2-APB inhibited SOCE in Caki-1 but enhanced it in Caki-2, suggesting Orai3 as the primary SOCE channel in pRCC. Knockdown of Orai1 and Orai3 reduced cell migration and proliferation via regulating focal adhesion kinase (FAK) and Cyclin D1 in both cell lines. These findings highlight the critical roles of Orai1 and Orai3 in RCC metastasis, with Orai3 linked to poorer prognosis in females with pRCC. This study offers valuable insights into RCC diagnostics and potential therapeutic strategies targeting ORAI channels and STIM proteins.
6.Progressive tooth pattern changes in Cilk1-deficient mice depending on Hedgehog signaling.
Minjae KYEONG ; Ju-Kyung JEONG ; Dinuka ADASOORIYA ; Shiqi KAN ; Jiwoo KIM ; Jieun SONG ; Sihyeon PARK ; Suyeon JE ; Seok Jun MOON ; Young-Bum PARK ; Hyuk Wan KO ; Eui-Sic CHO ; Sung-Won CHO
International Journal of Oral Science 2025;17(1):71-71
Primary cilia function as critical sensory organelles that mediate multiple signaling pathways, including the Hedgehog (Hh) pathway, which is essential for organ patterning and morphogenesis. Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice. Cilk1, a highly conserved serine/threonine-protein kinase localized within primary cilia, plays a critical role in ciliary transport. Loss of Cilk1 results in severe ciliopathy phenotypes, including polydactyly, edema, and cleft palate. However, the role of Cilk1 in tooth development remains unexplored. In this study, we investigated the role of Cilk1 in tooth development. Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars. Cilk1 deficiency resulted in altered ciliary dynamics, characterized by reduced frequency and increased length, accompanied by downregulation of Hh target genes, such as Ptch1 and Sostdc1, leading to the formation of diastemal supernumerary teeth. Furthermore, in Cilk1-/-;PCS1-MRCS1△/△ mice, which exhibit a compounded suppression of Hh signaling, we uncovered a novel phenomenon: diastemal supernumerary teeth can be larger than first molars. Based on these findings, we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning: initially inducing diastemal supernumerary teeth, then enlarging them, and ultimately leading to molar fusion. This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.
Animals
;
Hedgehog Proteins/physiology*
;
Mice
;
Signal Transduction/physiology*
;
Tooth, Supernumerary
;
Molar
;
Cilia/physiology*
;
Odontogenesis/physiology*
;
Patched-1 Receptor
;
Protein Serine-Threonine Kinases/physiology*
;
Mice, Knockout
;
Adaptor Proteins, Signal Transducing
7.Implant assisted removable partial denture with implant surveyed prostheses: A 9-year follow-up
Jae-Rim LEE ; Hyung-In YOON ; Hee-Sun KIM ; Hye-Young SIM ; Yoon-Sic HAN
The Journal of Korean Academy of Prosthodontics 2022;60(2):211-221
Implant placement may be restricted by anatomical and/or financial limitations in restoring a completely edentulous arch, or the patients’ unwillingness to have extensive surgical procedures. Implant assisted removable partial dentures (IARPD) in combination with anterior fixed implant prostheses can be proposed as an alternative treatment option for the restoration of a completely edentulous arch. In this case, a 56-year-old female patient who has a fully edentulous maxilla opposed by partially edentulous mandible was treated. The treatment option for the maxilla consisted of an implant-assisted removable partial denture supported by four anterior fixed implant prostheses. The mandible was restored with 8 anterior fixed partial dentures and posterior fixed implant-supported prostheses.Long-term follow-up and supportive periodontal treatment were performed for 9years, and the patient was satisfied with the overall appearance as well as masticatory function.
8.When do we need more than local compression to control intraoral haemorrhage?
Jun Bae SOHN ; Ho LEE ; Yoon Sic HAN ; Da Un JUNG ; Hye Young SIM ; Hee Sun KIM ; Sohee OH
Journal of the Korean Association of Oral and Maxillofacial Surgeons 2019;45(6):343-350
OBJECTIVES:
The aims of this study were to determine the effectiveness of local compression in patients presenting to the emergency room with intraoral bleeding and to identify when complex haemostatic measures may be required.
MATERIALS AND METHODS:
Five hundred forty patients who had experienced intraoral haemorrhage were retrospectively reviewed. The outcome variable was the haemostasis method used, i.e., simple (local compression with gauze) or complex (an alternative method after local compression has failed). Predictor variables were sex, age, American Society of Anesthesiologists (ASA) class, hepatic cirrhosis, bleeding disorder, use of antithrombotic agents, and site/cause of haemorrhage.
RESULTS:
The mean patient age was 48.9±23.9 years, 53.5% were male, 42.8% were ASA class II or higher, and 23.7% were taking antithrombotic agents. Local compression was used most often (68.1%), followed by local haemostatic agents, sutures, systemic tranexamic acid or blood products, and electrocautery. The most common site of bleeding was the gingiva (91.7%), and the most common cause was tooth extraction (45.7%). Risk factors for needing a complex haemostasis method were use of antithrombotic agents (odds ratio 2.047, P=0.009) and minor oral surgery (excluding extraction and implant procedures; odds ratio 6.081, P=0.001).
CONCLUSION
A haemostasis method other than local compression may be needed in patients taking antithrombotic agents or having undergone minor oral surgery.
9.Investigation of the association between orthodontic treatment and temporomandibular joint pain and dysfunction in the South Korean population
Hye Young SIM ; Hee Sun KIM ; Da Un JUNG ; Ho LEE ; Yoon Sic HAN ; Kyungdo HAN ; Kyoung In YUN
The Korean Journal of Orthodontics 2019;49(3):181-187
OBJECTIVE:
This study investigated the relationship between orthodontic treatment and temporomandibular disorders (TMD) in South Korean population.
METHODS:
This study obtained data from the 2012 Korean National Health and Nutrition Examination Survey. The final sample size was 5,567 participants who were ≥ 19 years of age. Logistic regression analysis was performed to evaluate the relationship between orthodontic treatment and TMD.
RESULTS:
Participants who underwent orthodontic treatment showed higher educational level, lower body mass index, reduced chewing difficulty, and reduced speaking difficulty. The adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) for orthodontic treatment and TMD were 1.614 (1.189–2.190), 1.573 (1.162–2.129) and 1.612 (1.182–2.196) after adjusting for age, sex and psychosocial factors. Adjusted ORs and their 95% CIs for orthodontic treatment and clicking were 1.778 (1.289–2.454), 1.742 (1.265–2.400) and 1.770 (1.280–2.449) after adjusting for confounding factors. However, temporomandibular joint pain and functional impairment was not associated with orthodontic treatment.
CONCLUSIONS
Temporomandibular joint pain and dysfunction was not associated with orthodontic treatment.
10.When do we need more than local compression to control intraoral haemorrhage?
Jun Bae SOHN ; Ho LEE ; Yoon Sic HAN ; Da Un JUNG ; Hye Young SIM ; Hee Sun KIM ; Sohee OH
Journal of the Korean Association of Oral and Maxillofacial Surgeons 2019;45(6):343-350
OBJECTIVES: The aims of this study were to determine the effectiveness of local compression in patients presenting to the emergency room with intraoral bleeding and to identify when complex haemostatic measures may be required.MATERIALS AND METHODS: Five hundred forty patients who had experienced intraoral haemorrhage were retrospectively reviewed. The outcome variable was the haemostasis method used, i.e., simple (local compression with gauze) or complex (an alternative method after local compression has failed). Predictor variables were sex, age, American Society of Anesthesiologists (ASA) class, hepatic cirrhosis, bleeding disorder, use of antithrombotic agents, and site/cause of haemorrhage.RESULTS: The mean patient age was 48.9±23.9 years, 53.5% were male, 42.8% were ASA class II or higher, and 23.7% were taking antithrombotic agents. Local compression was used most often (68.1%), followed by local haemostatic agents, sutures, systemic tranexamic acid or blood products, and electrocautery. The most common site of bleeding was the gingiva (91.7%), and the most common cause was tooth extraction (45.7%). Risk factors for needing a complex haemostasis method were use of antithrombotic agents (odds ratio 2.047, P=0.009) and minor oral surgery (excluding extraction and implant procedures; odds ratio 6.081, P=0.001).CONCLUSION: A haemostasis method other than local compression may be needed in patients taking antithrombotic agents or having undergone minor oral surgery.
Anticoagulants
;
Electrocoagulation
;
Emergency Service, Hospital
;
Emergency Treatment
;
Fibrinolytic Agents
;
Gingiva
;
Hemorrhage
;
Humans
;
Liver Cirrhosis
;
Male
;
Methods
;
Odds Ratio
;
Retrospective Studies
;
Risk Factors
;
Surgery, Oral
;
Sutures
;
Tooth Extraction
;
Tranexamic Acid

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