Autophagy and gastrointestinal cancers: the behind the scenes role of long non-coding RNAs in initiation, progression, and treatment resistance

Shafabakhsh, Rana; Arianfar, Farzaneh; Vosough, Massoud; Mirzaei, Hamid Reza; Mahjoubin‐Tehran, Maryam; Khanbabaei, Hashem; Kowsari, Hamed; Shojaie, Layla; Azar, Maryam Ebadi Fard; Hamblin, Michael R.; Mirzaei, Hamed

doi:10.1038/s41417-020-00272-7

Cited by 41 publications

(21 citation statements)

References 367 publications

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“…According to American Cancer Statistics 2021, there will be approximately 40,000 new cancer cases and 30,000 deaths per year, with a 5-year relative survival rate of only 20% [3]. HCC is a complex and multistage disease that may be explained by genetic and epigenetic changes [4][5][6][7][8]. Despite the development of surgery and combined treatment, as well as progress in early diagnosis and interventional therapy, most patients are still diagnosed in the advanced stage of HCC with a low 5-year survival rate and poor prognosis [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

LPCAT1 overexpression promotes the progression of hepatocellular carcinoma

et al. 2021

Cancer Cell Int

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Background Hepatocellular carcinoma (HCC) remains one of the most common malignant neoplasms. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) plays a key role in the lipid remodelling and is correlated with various neoplasms. Nonetheless, the biological functions and molecular mechanisms of LPCAT1 underlying HCC remain obscure. Methods In the present study, we investigated the role of LPCAT1 in the progression of HCC. In-house RT-qPCR, tissue microarrays, and immunohistochemistry were performed to detect the expression levels and the clinical value of LPCAT1 in HCC. External datasets were downloaded to confirm the results. Proliferation, migration, invasiveness, cell cycle, and apoptosis assays were conducted to reveal the biological effects LPCAT1 has on SMMC-7721 and Huh7 cells. HCC differentially expressed genes and LPCAT1 co-expressed genes were identified to explore the molecular mechanisms underlying HCC progression. Results LPCAT1 showed upregulated expression in 3715 HCC specimens as opposed to 3105 non-tumour specimens. Additionally, LPCAT1 might be an independent prognostic factor for HCC. LPCAT1-knockout hampered cellular proliferation, migration, and metastasis in SMMC-7721 and Huh7 cells. More importantly, the cell cycle and chemical carcinogenesis were the two most enriched signalling pathways. Conclusions The present study demonstrated that increased LPCAT1 correlated with poor prognosis in HCC patients and fuelled HCC progression by promoting cellular growth, migration, and metastasis.

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Section: Introductionmentioning

confidence: 99%

LPCAT1 overexpression promotes the progression of hepatocellular carcinoma

et al. 2021

Cancer Cell Int

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“… 3 A growing body of evidence has implicated lncRNAs in the progression of a series of cancers. 4 , 5 For example, lncRNAs can mediate the progression of gastrointestinal cancers by regulating autophagy 6 or promote tumor progression by rewiring metabolism. 7 lncRNAs were also found to regulate inflammatory reactions in sepsis-induced organ damage, and they might represent novel diagnostic markers for patients with sepsis.…”

Section: Introductionmentioning

confidence: 99%

The lncRNA CASC9 alleviates lipopolysaccharide-induced acute kidney injury by regulating the miR-424-5p/TXNIP pathway

Fan

Zhu

et al. 2021

J Int Med Res

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Objective This study aimed to clarify the mechanism by which the long non-coding RNA cancer susceptibility candidate 9 (CASC9) alleviates sepsis-related acute kidney injury (S-AKI). Methods A lipopolysaccharide (LPS)-induced AKI model was established to simulate S-AKI. HK-2 human renal tubular epithelial cells were treated with LPS to establish an in vitro model, and mice were intraperitoneally injected with LPS to generate an in vivo model. Subsequently, the mRNA expression of inflammatory and antioxidant factors was validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Reactive oxygen species (ROS) production was assessed using an assay kit. Apoptosis was detected by western blotting and fluorescence-activated cell sorting. Results CASC9 was significantly downregulated in the LPS-induced AKI model. CASC9 attenuated cell inflammation and apoptosis and enhanced the antioxidant capacity of cells. Regarding the mechanism, miR-424-5p was identified as the downstream target of CASC9, and the interaction between CASC9 and miR-424-5p promoted thioredoxin-interacting protein (TXNIP) expression. Conclusions CASC9 alleviates LPS-induced AKI in vivo and in vitro, and CASC9 directly targets miR-424-5p and further promotes the expression of TXNIP. We have provided a possible reference strategy for the treatment of S-AKI.

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“…Existing studies indicate that autophagy plays a dynamic role in cancer initiation, progression, as well as drug resistance, by regulating interactions between the tumor and tumor microenvironment (190)(191)(192)(193). There is increasing evidence that a large number of lncRNAs are obviously involved in PC autophagy (20,53,191,194,195). Identification of the mechanisms by which autophagy is activated in PC will help clarify PC pathogenesis (196).…”

Section: Lncrnas As Cernas Inducing Autophagymentioning

confidence: 99%

Long Noncoding Competing Endogenous RNA Networks in Pancreatic Cancer

et al. 2021

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Pancreatic cancer (PC) is a highly malignant disease characterized by insidious onset, rapid progress, and poor therapeutic effects. The molecular mechanisms associated with PC initiation and progression are largely insufficient, hampering the exploitation of novel diagnostic biomarkers and development of efficient therapeutic strategies. Emerging evidence recently reveals that noncoding RNAs (ncRNAs), including long ncRNAs (lncRNAs) and microRNAs (miRNAs), extensively participate in PC pathogenesis. Specifically, lncRNAs can function as competing endogenous RNAs (ceRNAs), competitively sequestering miRNAs, therefore modulating the expression levels of their downstream target genes. Such complex lncRNA/miRNA/mRNA networks, namely, ceRNA networks, play crucial roles in the biological processes of PC by regulating cell growth and survival, epithelial–mesenchymal transition and metastasis, cancer stem cell maintenance, metabolism, autophagy, chemoresistance, and angiogenesis. In this review, the emerging knowledge on the lncRNA-associated ceRNA networks involved in PC initiation and progression will be summarized, and the potentials of the competitive crosstalk as diagnostic, prognostic, and therapeutic targets will be comprehensively discussed.

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Autophagy and gastrointestinal cancers: the behind the scenes role of long non-coding RNAs in initiation, progression, and treatment resistance

Cited by 41 publications

References 367 publications

LPCAT1 overexpression promotes the progression of hepatocellular carcinoma

LPCAT1 overexpression promotes the progression of hepatocellular carcinoma

The lncRNA CASC9 alleviates lipopolysaccharide-induced acute kidney injury by regulating the miR-424-5p/TXNIP pathway

Long Noncoding Competing Endogenous RNA Networks in Pancreatic Cancer

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