&lt;p&gt;LACTB Regulates PIK3R3 to Promote Autophagy and Inhibit EMT and Proliferation Through the PI3K/AKT/mTOR Signaling Pathway in Colorectal Cancer&lt;/p&gt;

Xu, Wei; Yu, Minhao; Qin, Jun; Luo, Yang; Zhong, Ming

doi:10.2147/cmar.s250661

Cited by 45 publications

(63 citation statements)

References 62 publications

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“…Subsequently, rescue experiments also showed that the miR-193a-5p inhibitor restored the inhibitory effect of knocking down circRNA_0000392 on cell proliferation and restored the inhibition of this pathway by downregulation of circRNA_0000392. Abnormal activation of AKT-mTOR signaling pathway plays an important role in the malignant progression of CRC [40][41][42].…”

Section: Discussionmentioning

confidence: 99%

CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis

Liu

Cheng

et al. 2020

Preprint

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Background: Circular RNAs (circRNAs), important members of the noncoding RNA family, have been recently revealed to play a role in the pathogenic progression of diseases, particularly in the malignant progression of cancer. With the application of high-throughput sequencing technology, a large number of circRNAs have been identified in tumor tissues, and some circRNAs have been demonstrated to act as oncogenes. In this study, we analyzed the circRNA expression profile in colorectal cancer (CRC) tissues and normal adjacent tissues by high-throughput sequencing. We focused on circRNA_0000392, a circRNA with significantly increased expression in CRCtissues, and further investigated its function in the progression of colorectal cancer.Methods: The expression profile of circRNAs in 6 pairs of CRC tissues and normal adjacent tissues was analyzed by RNA sequencing. We verified the identified differentially expressed circRNAs in additional samples by qRT-PCR and selected circRNA_0000392 to evaluate its associations with clinicopathological features. Then, we knocked down circRNA_0000392 in CRC cells and investigated the in vitro and in vivo effects using functional experiments. Dual luciferase and RNA pull-down assays were performed to further explore the downstream potential molecular mechanisms.Results: CircRNA_0000392 was significantly upregulated in CRC compared with normal adjacent tissues and cell lines. The expression level of circRNA_0000392 was positively correlated with the malignant progression of CRC. Functional studies revealed that reducing the expression of circRNA_0000392 could inhibit the proliferation and invasion of CRC both in vitro and in vivo. Mechanistically, circRNA_0000392 could act as a sponge of miR-193a-5p and regulate the expression of PIK3R3, affecting the activation of the AKT-mTOR pathway in CRC cells.Conclusions: CircRNA_0000392 functions as an oncogene through the miR-193a-5p/PIK3R3/Akt axis in CRC cells, suggesting that circRNA_0000392 is a potential therapeutic target for the treatment of colorectal cancer and a predictive marker for CRC patients.

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Section: Discussionmentioning

confidence: 99%

CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis

Liu

Cheng

et al. 2020

Preprint

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“…Colon cancer is one of the deadliest, most common and increasingly prevalent malignancies, and it currently has the second-highest rate of cancer-related deaths worldwide. [1][2][3] Despite the development of methods for early diagnosis and molecular therapeutic targets for colon cancer, the mortality rate among colon cancer patients remains high, making the development of more sensitive and specific diagnostic molecules, biomarkers, and therapeutic targets extremely urgent. 1,4,5 Serine beta-lactamase-like protein (LACTB) is a mitochondrial protein that is most commonly expressed in the skeletal muscles, heart, and liver in mammals.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] Despite the development of methods for early diagnosis and molecular therapeutic targets for colon cancer, the mortality rate among colon cancer patients remains high, making the development of more sensitive and specific diagnostic molecules, biomarkers, and therapeutic targets extremely urgent. 1,4,5 Serine beta-lactamase-like protein (LACTB) is a mitochondrial protein that is most commonly expressed in the skeletal muscles, heart, and liver in mammals. [6][7][8] It has been reported that LACTB is likely to regulate oxidative phosphorylation and mitochondrial lipid metabolism, thereby influencing tumor progression by influencing mitochondrial membrane tissue and microencapsulation.…”

Section: Introductionmentioning

confidence: 99%

“…[6][7][8] It has been reported that LACTB is likely to regulate oxidative phosphorylation and mitochondrial lipid metabolism, thereby influencing tumor progression by influencing mitochondrial membrane tissue and microencapsulation. 1,9 Studies have shown that LACTB has a strong inhibitory effect on a variety of tumors, including breast cancer, glioma, and colorectal cancer. 1 LACTB can inhibit the epithelial-tomesenchymal transition (EMT) and cell proliferation of breast cancer and colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

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<p>MicroRNA-1276 Promotes Colon Cancer Cell Proliferation by Negatively Regulating LACTB</p>

Wang¹,

Shi²,

Hong³

et al. 2020

CMAR

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LACTB, regulated by a variety of microRNAs (miRNAs), is proven to be a tumor suppressor. However, there are few reports that LACTB in colon cancer cells is regulated by miRNA. Therefore, the aim of this study was to explore the miRNAs that regulate LACTB in colon cancer. Patients and Methods: Data from TCGA were analyzed in starBase and GEPIA2, and Western blot and quantitative PCR (qPCR) were used to detect the expression of LACTB in colon cancer cell lines. MiRNAs targeting LACTB were predicted by MicroT-CDS, starBase, miRDB, mirDIP, and DIANA. The relationship between LACTB and miRNA was explored by dual-luciferase assay. MTT, propidium iodide (PI), Western blot, Annexin V-FITC/PI Kit, qPCR and transwell assay were used to detect the changes in cell proliferation, cell cycle, autophagy, apoptosis, epithelial-to-mesenchymal transition (EMT), cell migration, and invasiveness in colon cancer cells that overexpressed miR-1276 and/or LACTB. Results: The results showed that the LACTB mRNA level was lower and the miR-1276 level was higher in colon cancer than in normal tissue. MiR-1276 inhibited the expression of LACTB. Furthermore, overexpression of miR-1276 in colon cancer cells increased proliferation, migration, invasiveness and EMT, and decreased autophagy and apoptosis. Supplementing LACTB suppressed these effects of miR-1276. Conclusion: In conclusion, miR-1276, which may be a potential therapy for colon cancer, inhibits cell growth and promotes apoptosis by targeting LACTB in colon cancer cells.

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Section: Discussionmentioning

confidence: 99%

CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis

Liu

Cheng

et al. 2020

J Exp Clin Cancer Res

103

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Background Circular RNAs (circRNAs), important members of the noncoding RNA family, have been recently revealed to play a role in the pathogenic progression of diseases, particularly in the malignant progression of cancer. With the application of high-throughput sequencing technology, a large number of circRNAs have been identified in tumor tissues, and some circRNAs have been demonstrated to act as oncogenes. In this study, we analyzed the circRNA expression profile in colorectal cancer (CRC) tissues and normal adjacent tissues by high-throughput sequencing. We focused on circRNA_0000392, a circRNA with significantly increased expression in CRCtissues, and further investigated its function in the progression of colorectal cancer. Methods The expression profile of circRNAs in 6 pairs of CRC tissues and normal adjacent tissues was analyzed by RNA sequencing. We verified the identified differentially expressed circRNAs in additional samples by qRT-PCR and selected circRNA_0000392 to evaluate its associations with clinicopathological features. Then, we knocked down circRNA_0000392 in CRC cells and investigated the in vitro and in vivo effects using functional experiments. Dual luciferase and RNA pull-down assays were performed to further explore the downstream potential molecular mechanisms. Results CircRNA_0000392 was significantly upregulated in CRC compared with normal adjacent tissues and cell lines. The expression level of circRNA_0000392 was positively correlated with the malignant progression of CRC. Functional studies revealed that reducing the expression of circRNA_0000392 could inhibit the proliferation and invasion of CRC both in vitro and in vivo. Mechanistically, circRNA_0000392 could act as a sponge of miR-193a-5p and regulate the expression of PIK3R3, affecting the activation of the AKT-mTOR pathway in CRC cells. Conclusions CircRNA_0000392 functions as an oncogene through the miR-193a-5p/PIK3R3/Akt axis in CRC cells, suggesting that circRNA_0000392 is a potential therapeutic target for the treatment of colorectal cancer and a predictive marker for CRC patients.

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<p>LACTB Regulates PIK3R3 to Promote Autophagy and Inhibit EMT and Proliferation Through the PI3K/AKT/mTOR Signaling Pathway in Colorectal Cancer</p>

Cited by 45 publications

References 62 publications

CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis

CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis

<p>MicroRNA-1276 Promotes Colon Cancer Cell Proliferation by Negatively Regulating LACTB</p>

CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis

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