Knockdown of SLCO4C1 inhibits cell proliferation and metastasis in endometrial cancer through inactivating the PI3K/Akt signaling pathway

Hu, Xiang; Han, Tong; Bian, Yiding; Tong, Huan; Xu, Wen; Li, Yiran; Wan, Xiaoping

doi:10.3892/or.2020.7478

Cited by 16 publications

(19 citation statements)

References 25 publications

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“…[30][31][32] Meanwhile, the PI3K/AKT signaling pathway takes part in tumor metastasis. 33 Intriguingly, it has been reported that PI3K/ AKT signaling pathway can be regulated by lncRNAs. 34,35 TM4SF1-AS1 is located on chromosome 3q25.1 region and is the antisense RNA of TM4SF1.…”

Section: Discussionmentioning

confidence: 99%

<p>lncRNA TM4SF1-AS1 Activates the PI3K/AKT Signaling Pathway and Promotes the Migration and Invasion of Lung Cancer Cells</p>

Zhou¹,

Wang²,

Chi³

et al. 2020

CMAR

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Metastasis is a crucial cause of the high mortality in patients with lung cancer. Long non-coding RNAs (lncRNAs) are emerging as important players in the development and progression of human cancers. Here, we aimed to identify metastasis-associated lncRNA and to study its roles in the migration and invasion of lung cancer cells. Materials and Methods: We screened differentially expressed lncRNAs between high-and low-metastatic lung cancer cell lines by using microarray and identified the target lncRNA TM4SF1-AS1. The effect of the TM4SF1-AS1 on the invasion and migration was evaluated through the wound healing experiment and transwell assay. The expression of related genes was assessed by RNA sequence and Western blotting. Results: TM4SF1-AS1 was highly expressed in high metastatic lung cancer cell line, and it was also significantly up-regulated in lymph node metastatic lung cancer and was associated with lymph node metastasis. Overexpression of TM4SF1-AS1 promoted the migration and invasion of lung cancer cells. Overexpression of TM4SF1-AS1 decreased the expression of E-Cadherin and increased the expression of Vimentin, Snail and Twist, while knockdown of TM4SF1-AS1 exhibited the opposite trend. Furthermore, RNA sequence analysis revealed that some signaling pathways, including PI3K/AKT signaling pathway, were enriched upon TM4SF1-AS1 overexpression. Western blotting further confirmed that the PI3K/AKT signaling pathway was activated by TM4SF1-AS1. Conclusion: This study illustrates that TM4SF1-AS1 promotes the migration and invasion of lung cancer cells by activating the PI3K/AKT signaling pathway. TM4SF1-AS1 might be a novel target of molecular treatment for lung cancer.

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Section: Discussionmentioning

confidence: 99%

<p>lncRNA TM4SF1-AS1 Activates the PI3K/AKT Signaling Pathway and Promotes the Migration and Invasion of Lung Cancer Cells</p>

Zhou¹,

Wang²,

Chi³

et al. 2020

CMAR

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“…There are very limited data available about expression of SLC51B and SLC51A in cancer [ 45 ]. Interestingly, OATP1B3 and OATP4C1 are the only E1-S transporters that have previously been investigated in EC tissue [ 28 , 47 ]. The levels of OATP4C1 were found to be higher in EC compared to normal endometrial tissue where the expression of SLCO4C1 correlates positively with disease progression [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, OATP1B3 and OATP4C1 are the only E1-S transporters that have previously been investigated in EC tissue [ 28 , 47 ]. The levels of OATP4C1 were found to be higher in EC compared to normal endometrial tissue where the expression of SLCO4C1 correlates positively with disease progression [ 47 ]. We observed no difference in SLCO4C1 expression in EC versus adjacent control tissues and found no association with any of the prognostic factors probably due to the fact that our cohort included mostly low-grade EC samples (26 low grade and 10 high grade).…”

Section: Discussionmentioning

confidence: 99%

Altered Profile of E1-S Transporters in Endometrial Cancer: Lower Protein Levels of ABCG2 and OSTβ and Up-Regulation of SLCO1B3 Expression

Pavlič

Vidic

Anko

et al. 2021

IJMS

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Endometrial cancer (EC) is associated with increased estrogen actions. Locally, estrogens can be formed from estrone-sulphate (E1-S) after cellular uptake by organic anion-transporting polypeptides (OATP) or organic anion transporters (OAT). Efflux of E1-S is enabled by ATP Binding Cassette transporters (ABC) and organic solute transporter (OST)αβ. Currently, 19 E1-S transporters are known but their roles in EC are not yet understood. Here, we analysed levels of E1-S transporters in Ishikawa (premenopausal EC), HEC-1-A (postmenopausal EC), HIEEC (control) cell lines, in EC tissue, examined metabolism of steroid precursor E1-S, studied effects of OATPs’ inhibition and gene-silencing on E1-S uptake, and assessed associations between transporters and histopathological data. Results revealed enhanced E1-S metabolism in HEC-1-A versus Ishikawa which could be explained by higher levels of OATPs in HEC-1-A versus Ishikawa, especially 6.3-fold up-regulation of OATP1B3 (SLCO1B3), as also confirmed by immunocytochemical staining and gene silencing studies, lower ABCG2 expression and higher levels of sulfatase (STS). In EC versus adjacent control tissue the highest differences were seen for ABCG2 and SLC51B (OSTβ) which were 3.0-fold and 2.1-fold down-regulated, respectively. Immunohistochemistry confirmed lower levels of these two transporters in EC versus adjacent control tissue. Further analysis of histopathological data indicated that SLCO1B3 might be important for uptake of E1-S in tumours without lymphovascular invasion where it was 15.6-fold up-regulated as compared to adjacent control tissue. Our results clearly indicate the importance of E1-S transporters in EC pathophysiology and provide a base for further studies towards development of targeted treatment.

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“…Altered OATP4C1 expression has been linked to CVD events [ 146 , 243 ] ( Table 4 ) and endometrial cancer tissues [ 209 ], and genetic variants of the SLCO4C1 gene were also found to be associated with obesity [ 244 ]. Increased expression of human OATP4C1 in a transgenic rat kidney model leads to an increased excretion of uremic toxins and reduced hypertension and cardiomegaly [ 146 , 243 ].…”

Section: Transporter Families Shown To Transport L-arginine And/ormentioning

confidence: 99%

Transport of L-Arginine Related Cardiovascular Risk Markers

Banjarnahor

Rodionov

König

et al. 2020

JCM

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L-arginine and its derivatives, asymmetric and symmetric dimethylarginine (ADMA and SDMA) and L-homoarginine, have emerged as cardiovascular biomarkers linked to cardiovascular outcomes and various metabolic and functional pathways such as NO-mediated endothelial function. Cellular uptake and efflux of L-arginine and its derivatives are facilitated by transport proteins. In this respect the cationic amino acid transporters CAT1 and CAT2 (SLC7A1 and SLC7A2) and the system y+L amino acid transporters (SLC7A6 and SLC7A7) have been most extensively investigated, so far, but the number of transporters shown to mediate the transport of L-arginine and its derivatives is constantly increasing. In the present review we assess the growing body of evidence regarding the function, expression, and clinical relevance of these transporters and their possible relation to cardiovascular diseases.

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Knockdown of SLCO4C1 inhibits cell proliferation and metastasis in endometrial cancer through inactivating the PI3K/Akt signaling pathway

Cited by 16 publications

References 25 publications

<p>lncRNA TM4SF1-AS1 Activates the PI3K/AKT Signaling Pathway and Promotes the Migration and Invasion of Lung Cancer Cells</p>

<p>lncRNA TM4SF1-AS1 Activates the PI3K/AKT Signaling Pathway and Promotes the Migration and Invasion of Lung Cancer Cells</p>

Altered Profile of E1-S Transporters in Endometrial Cancer: Lower Protein Levels of ABCG2 and OSTβ and Up-Regulation of SLCO1B3 Expression

Transport of L-Arginine Related Cardiovascular Risk Markers

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