LncRNA PINK1-AS promotes Gαi1-driven gastric cancer tumorigenesis by sponging microRNA-200a

Lv, Yan; Yin, Wei; Yu, Shizhu; Wang, Shusheng; Cheng, Kai-Wen; Zhang, Zhiqing; Yao, Jin; Zhou, Li-Na; Ling, Zhuoyan; Cao, Cong

doi:10.1038/s41388-021-01812-7

Cited by 26 publications

(22 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our previous studies have shown that Gαi proteins associated with several oncogenic RTKs (EGFR, VEGFR2, TrkB, FGFR and KGFR), mediating downstream signaling activation 14 , 16 - 21 . Co-IP (co-immunoprecipitation) assays, Figure 6A , demonstrated that Gαi3 immunoprecipitated with VEGFR2, FGFR, PGDFR and EGFR in primary OS cells (“pOS-1/2”) and immortalized U2OS cells.…”

Section: Resultsmentioning

confidence: 99%

“…The cell viability detection by cell counting kit-8 (CCK-8), the EdU nuclear staining assaying of cell proliferation, propidium iodide (PI)-FACS, “Transwell” assays were carried out using the previously described protocols 18 , 21 , 25 , 29 - 33 .…”

Section: Methodsmentioning

confidence: 99%

“…Apoptosis-related assays, including the TUNEL nuclear staining, 7-AAD and Annexin V double staining, caspase-3/-9 activities measurement, and ELISA testing the cellular ssDNA (single strand DNA) contents were described early 21 , 25 , 31 - 33 .…”

Section: Methodsmentioning

confidence: 99%

“…Similarly, Gαi1/3 mediated BDNF (brain-derived neurotrophic factor)-stimulated Akt-mTOR activation 17 . Therefore, by mediating signaling transduction of multiple RTKs, Gαi proteins could be important oncogenic genes and therapeutic targets for human cancer 14 , 18 , 21 . Indeed, we have previously shown that Gαi proteins are upregulated in glioma and gastric cancers, required for cancer growth 14 , 18 , 21 .…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, by mediating signaling transduction of multiple RTKs, Gαi proteins could be important oncogenic genes and therapeutic targets for human cancer 14 , 18 , 21 . Indeed, we have previously shown that Gαi proteins are upregulated in glioma and gastric cancers, required for cancer growth 14 , 18 , 21 . The current study explored Gαi3 expression and potential functions in human OS.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Identification of Gαi3 as a promising target for osteosarcoma treatment

Bian¹,

Shan²,

Zhu³

et al. 2022

Int. J. Biol. Sci.

Self Cite

View full text Add to dashboard Cite

Sustained activation of multiple receptor tyrosine kinases (RTKs) simultaneously is vital for tumorigenesis and progression of osteosarcoma (OS). Gαi proteins recruitment to various RTKs mediates downstream oncogenic signaling activation. The expression, functions and underlying mechanisms of Gαi3 in human OS were examined. Expression of Gαi3 is robustly elevated in human OS tissues and is correlated with a poor overall survival. In patient-derived primary OS cells and immortalized lines (MG63 and U2OS), Gαi3 depletion, by shRNA and CRISPR/Cas9 strategies, robustly suppressed cell viability, proliferation and migration, while provoking G1-S arrest and apoptosis activation. Conversely, Gαi3 overexpressing ectopically can accelerate proliferation and migration of OS cells. In OS cells, Gαi3 immunoprecipitated with VEGFR2, FGFR, PGDFR and EGFR, mediating downstream cascade transduction. Akt-mTOR activation in primary OS cells was potently inhibited by Gαi3 shRNA, knockout or dominant negative mutation, but augmented after Gαi3 overexpression. In vivo studies showed that Gαi3 shRNA AAV (adeno-associated viruses) intratumoral injection largely inhibited the growth of subcutaneous xenografts of primary OS cells. Moreover, the growth of the Gαi3-knockout primary OS xenografts was much slower than that of OS xenografts with empty vector. In Gαi3-depleted OS xenografts tissues, Gαi3 downregulation and Akt-mTOR inactivation were detected. Taken together, overexpressed Gαi3 mediates RTK-Akt signaling to drive OS progression.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Identification of Gαi3 as a promising target for osteosarcoma treatment

Bian¹,

Shan²,

Zhu³

et al. 2022

Int. J. Biol. Sci.

Self Cite

View full text Add to dashboard Cite

show abstract

LINC00355 promotes gastric carcinogenesis by scaffolding p300 to activate CDC42 transcription and enhancing HNRNPA2B1 to stabilize CDC42 mRNA dependent on m6A

Chen,

Xiao,

Xie

et al. 2023

Molecular Carcinogenesis

View full text Add to dashboard Cite

LINC00355 is involved in the tumorigenesis of several types of cancer. We verified that LINC00355 is upregulated in gastric cancer (GC) and contributes to GC cells' proliferation and metastasis. RNA sequencing (RNA‐seq) and rescue assays suggested that LINC00355 controls gastric carcinogenesis by regulating the expression of cell division cycle 42 (CDC42) guanosine triphosphatase (GTPases), thereby activating their downstream pathways. Most previous studies have shown that LINC00355 acts as a ceRNA by sponging miRNAs to modulate downstream gene expression. Our group focus on epigenetic regulatory potential of LINC00355 in gene expression. Mechanistically, LINC00355 binds to p300 histone acetyltransferase, specifying the histone modification pattern on the CDC42 promoter to activate CDC42 transcription, thereby altering GC cell biology. In addition, HNRNPA2B1, which is upregulated by LINC00355, recognizes the N6‐methyladenosine (m6A) sites of CDC42 and enhances the stability of CDC42 mRNA transcripts. Therefore, LINC00355 is mechanistically, functionally, and clinically oncogenic in GC cells.

show abstract

LAMC2 regulates the proliferation, invasion, and metastasis of gastric cancer via PI3K/Akt signaling pathway

Cheng,

Li,

Dong

et al. 2024

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

Objectives Gastric cancer (GC) is a prevalent malignant tumor widely distributed globally, exhibiting elevated incidence and fatality rates. The gene LAMC2 encodes the laminin subunit gamma-2 chain and is found specifically in the basement membrane of epithelial cells. Its expression is aberrant in multiple types of malignant tumors. This research elucidated a link between LAMC2 and the clinical characteristics of GC and investigated the potential involvement of LAMC2 in GC proliferation and advancement. Materials and methods LAMC2 expressions were detected in GC cell lines and normal gastric epithelial cell lines via qRT-PCR. Silencing and overexpression of the LAMC2 were conducted by lentiviral transfection. A xenograft mouse model was also developed for in vivo analysis. Cell functional assays were conducted to elucidate the involvement of LAMC2 in cell growth, migration, and penetration. Further, immunoblotting was conducted to investigate the impact of LAMC2 on the activation of signal pathways after lentiviral transfection. Results In the findings, LAMC2 expression was markedly upregulated in GC cell lines as opposed to normal gastric epithelial cells. In vitro analysis showed that sh-LAMC2 substantially inhibited GC cell growth, migration, and invasion, while oe-LAMC2 displayed a contrasting effect. Xenograft tumor models demonstrated that oe-LAMC2 accelerated tumor growth via high expression of Ki-67. Immunoblotting analysis revealed a substantial decrease in various signaling pathway proteins, PI3K, p-Akt, and Vimentin levels upon LAMC2 knockdown, followed by increased E-cadherin expression. Conversely, its overexpression exhibited contrasting effects. Besides, epithelial-mesenchymal transition (EMT) was accelerated by LAMC2. Conclusion This study provides evidence indicating that LAMC2, by stimulating signaling pathways, facilitated EMT and stimulated the progression of GC cells in laboratory settings and mouse models. Research also explored that the abnormal LAMC2 expression acts as a biomarker for GC.

show abstract

LncRNA PINK1-AS promotes Gαi1-driven gastric cancer tumorigenesis by sponging microRNA-200a

Cited by 26 publications

References 49 publications

Identification of Gαi3 as a promising target for osteosarcoma treatment

Identification of Gαi3 as a promising target for osteosarcoma treatment

LINC00355 promotes gastric carcinogenesis by scaffolding p300 to activate CDC42 transcription and enhancing HNRNPA2B1 to stabilize CDC42 mRNA dependent on m6A

LAMC2 regulates the proliferation, invasion, and metastasis of gastric cancer via PI3K/Akt signaling pathway

Contact Info

Product

Resources

About