Long non-coding RNA HOTTIP affects renal cell carcinoma progression by regulating autophagy via the PI3K/Akt/Atg13 signaling pathway

Yang, Shuxu; Lu, Jingxiao; Chen, Xianguo; Liang, Chaozhao; Luo, Pengfei; Qin, Cong; Zhang, Jie

doi:10.1007/s00432-018-2808-0

Cited by 42 publications

(28 citation statements)

References 53 publications

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“…PI3K/Akt/Raptor pathway is also closely related to autophagy in cells. Cellular-myelocytomatosis viral oncogene(c-MYC) and Rat sarcoma (RAS), which are downstream transcription factors, are associated with the regulation of autophagy (Shaw and Cantley 2006), while Autophagy related gene 13 (ATG13) is directly involved in the regulation of autophagy (Su et al 2019). Some studies have confirmed that autophagy has a tumor suppressing function, and autophagy is turned off during tumor formation, which also causes autophagy inhibition of tumor growth to be shut down (Mizushima et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Aspirin has a better effect on PIK3CA mutant colorectal cancer cells by PI3K/Akt/Raptor pathway

Chen

Wang

Dong

et al. 2020

Mol Med

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Background: Aspirin, as a non-steroidal anti-inflammatory drug, can improve the survival rate of patients with colorectal cancer, while aspirin is effective in patients with PIK3CA mutant colorectal cancer (CRC). However, the mechanism of aspirin in the treatment of PIK3CA mutated CRC patients remains unclear. Methods: In this study, immunohistochemistry was used to detect the expression levels of PI3K and Raptor in colorectal cancer patients with PIK3CA mutation and PIK3CA wild-type patients. To demonstrate that aspirin has a better effect on the CRC of PIK3CA mutations in association with the PI3K/Akt/Raptor pathway, we used aspirin to treat PIK3CA mutant CRC cells (HCT-116 and RKO). Subsequently, the CCK8 assay and flow cytometry assay were used to detect the apoptosis of PIK3CA mutant CRC cells before and after aspirin use. Western blot was used to detect the changes of PI3K/Akt/Raptor-associated protein, autophagy protein microtubule associated protein 1 light chain 3 alpha (MAP1LC3A, LC3), beclin 1 (BECN1) and apoptosis protein BCL2-associated X protein/ BCL2 apoptosis regulator (Bax/Bcl2), Caspase 3 after treatment of CRC cells with PIK3CA mutation by aspirin. Results: Phosphoinositide-3-kinase (PI3K) and regulatory associated protein of MTOR complex 1 (Raptor) protein expression levels were higher in PIK3CA-mutant patients than in IK3CA wild-type patients. The expression of Bax/ Bcl2 increased after treatment indicates that aspirin can induce apoptosis of PIK3CA-mutant CRC cells. The expression level of MAP1LC3 (LC3) in cells increases with the concentration of aspirin demonstrates that aspirin can induce autophagy in CRC cells. After 48 h of treatment with aspirin, the phosphorylation of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) and ribosomal protein S6 kinase B1 (S6K1) was reduced, cell proliferation has been inhibited. After treatment with aspirin, as phosphorylation of PI3K and Protein kinase B (PKB, Akt) was decreased, Raptor expression was also decreased.Conclusion: Aspirin can regulate the proliferation, apoptosis and autophagy of CRC cells through the PI3K/Akt/ Raptor pathway, affecting PIK3CA-mutant CRC.

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Section: Discussionmentioning

confidence: 99%

Aspirin has a better effect on PIK3CA mutant colorectal cancer cells by PI3K/Akt/Raptor pathway

Chen

Wang

Dong

et al. 2020

Mol Med

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“…These results suggest that HOTTIP may participate in the pathogenesis of Hypo by regulating the proliferation of NT2. In tumor‐related studies, HOTTIP has been proved to participate in the pathogenesis of many tumors including endometrial cancer (Guan, Zhang, Zhang, Liu, & Ren, ), ovarian cancer (Zou, Wang, Gao, & Liang, ), and renal cell carcinoma (Su et al, ) by promoting tumor cell proliferation level. To further verify our hypothesis, the changes in cell function of NT2 and 293T after knocking down and overexpressing HOTTIP in vitro were monitored.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA HOTTIP is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation

Zhou

Zhang

et al. 2019

Molec Gen & Gen Med

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Background It has been proposed that lncRNAs, widely transcribed from genomes, play pivotal regulatory roles in a variety of biological processes, but their function in regulating spermatogenesis in human males is rarely reported. Methods QRT‐PCR was adopted to detect HOTTIP expression level in testicular tissues from hypospermatogenesis (Hypo) patients or controls. The proliferation levels of NT2 and 293T were measured via CCK‐8 and EdU detection. Meanwhile, luciferase reporter gene assay and bioinformatics analysis were carried out to identify a target of HOTTIP. Additionally, the underlying mechanism of HOTTIP’s function was investigated using western blotting and RIP analysis. Results The research results manifested that the expression of HOTTIP in testicular tissues from Hypo patients was prominently reduced in comparison with that in control testicular tissues. Interestingly, it was noted that HOTTIP exhibited a high expression in testicular embryonal carcinoma cell line NT2 compared with that in normal control cell line 293T. It was denoted in cell function evaluation that cell proliferation was impeded by downregulated HOTTIP but evidently stimulated by overexpressed HOTTIP. Moreover, HOTTIP was capable of positively modulating HOXA13 expression via the competitive binding to miR‐128‐3p. Conclusion Therefore, HOTTIP acting as ceRNAs to promote testicular embryonal carcinoma cell proliferation.

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“…Several other lncRNAs were identified who's dysfunction lead to the renal cancer cell proliferation, invasion and migration. In particular, increased expression of RCCRT1 [23], SPRY4-IT1 [24], H19 [25], and MALAT1 [21,26], HOTTIP [27] were associated with poor prognosis. Whereas decrease expression of CADM1-AS1 [28], NBAT-1 [29,30], lnc-ZNF180-2 [31], NONHSAT123350 [32], downregulate RNA in androgen independent cells (DRAIC) [33], and EPB41L4A-AS2 [34] were related to poor prognosis ( Table 1).…”

Section: Long Noncoding Rnas As Biomarker In Renal Cell Carcinomamentioning

confidence: 99%

Noncoding RNAs and Its Implication as Biomarkers in Renal Cell Carcinoma: A Systematic Analysis

Verma¹,

Gupta²

2019

ann urol oncol

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Renal cell carcinoma (RCC) is one of the most devastating disease with higher mortality rates. It comprises several subtypes exhibiting distinct histological features and clinical staging. Despite recent advancement in understanding the biology of RCC success in treatment rates remains dismal. This may be partly due to lack of specific biomarkers for early detection/prognosis and poor clinical outcome. Noncoding protein transcripts in the genome play important role in the initiation, evolution and progression of cancer. With the advancement in genomic analysis techniques, especially next-generation sequencing, a large number of new transcripts have been discovered, leading to better understanding of coding and noncoding RNAs. In the present review, we summarize recent advancement on renal cancer associated noncoding RNAs which includes long noncoding RNAs, microRNAs, and circular RNAs for their involvement in RCC along with their clinical implication as prognostic and diagnosis biomarkers.

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Long non-coding RNA HOTTIP affects renal cell carcinoma progression by regulating autophagy via the PI3K/Akt/Atg13 signaling pathway

Cited by 42 publications

References 53 publications

Aspirin has a better effect on PIK3CA mutant colorectal cancer cells by PI3K/Akt/Raptor pathway

Aspirin has a better effect on PIK3CA mutant colorectal cancer cells by PI3K/Akt/Raptor pathway

Long noncoding RNA HOTTIP is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation

Noncoding RNAs and Its Implication as Biomarkers in Renal Cell Carcinoma: A Systematic Analysis

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