Abstract 1490: MiR-21 has strong prognostic implications and functions as an oncogenic miR by modulating PI3K/Akt pathway at multiple levels in diffuse large B cell lymphoma

TUC338 is emerging as a novel vital long noncoding RNA (lncRNA) in human cancer; however, its role in diffuse large B cell lymphoma (DLBCL) remains unknown. In this study, we found that TUC338 was remarkably upregulated in DLBCL tissues as compared to matched normal tissues. High TUC338 was closely related to advanced Ann Arbor stage, resistance to CHOP-like treatment, and high IPI (International Prognostic Index). Stable knockdown of TUC338 evidently inhibited cell proliferation and chemotherapy resistance to Adriamycin and induced apoptosis. Further, we found that TUC338 was able to directly bind to miR-28-5p and increased EGFR level, resulting in activating carcinogenic PI3K/AKT signaling, thereby facilitating DLBCL uncontrolled growth. Moreover, we also found that depletion of TUC338 led to the inactivation of EGFR/PI3K/AKT pathway in vivo by using the xenograft tumor model. Preclinically, DLBCL patients with high TUC338 had shorter survival time than those with low TUC338, and serum TUC338 level was identified as an excellent indicator for DLBCL diagnosis. In sum, our findings clearly indicate that TUC338 functions as an oncogenic lncRNA in DLBCL through activating EGFR/PI3K/AKT pathway via sponging and inhibiting miR-28-5p, which may be a promising target for DLBCL treatment.

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Prognostic implications of 5-hydroxymethylcytosines from circulating cell-free DNA in diffuse large B-cell lymphoma

Blood Advances ◽

10.1182/bloodadvances.2019000175 ◽

2019 ◽

Vol 3 (19) ◽

pp. 2790-2799 ◽

Cited By ~ 3

Author(s):

Brian C.-H. Chiu ◽

Zhou Zhang ◽

Qiancheng You ◽

Chang Zeng ◽

Elizabeth Stepniak ◽

...

Keyword(s):

Prognostic Factors ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Free Dna ◽

Large B Cell Lymphoma ◽

Genome Wide ◽

Key Points ◽

Prognostic Implications ◽

Large B Cell

Key Points Genome-wide 5hmC loci can be profiled in 1 to 2 ng of cfDNA from blood plasma and correlate with clinical features of DLBCL. 5hmC in cfDNA collected at the time of DLBCL diagnosis is associated with EFS and OS, independent of established prognostic factors.

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Role of phosphatidylinositol 3′-kinase/AKT pathway in diffuse large B-cell lymphoma survival

Blood ◽

10.1182/blood-2006-04-016907 ◽

2006 ◽

Vol 108 (13) ◽

pp. 4178-4186 ◽

Cited By ~ 177

Author(s):

Shahab Uddin ◽

Azhar R. Hussain ◽

Abdul K. Siraj ◽

Pulicat S. Manogaran ◽

Naif A. Al-Jomah ◽

...

Keyword(s):

B Cell ◽

Cell Lines ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Akt Pathway ◽

Phosphatidylinositol 3 Kinase ◽

Large B Cell Lymphoma ◽

Induced Apoptosis ◽

Large B Cell

Abstract Phosphatidylinositol 3′-kinase (PI3K) is a key player in cell-growth signaling in a number of lymphoid malignancies, but its role in diffuse large B-cell lymphoma (DLBCL) has not been fully elucidated. Therefore, we investigated the role of the PI3K/AKT pathway in a panel of 5 DLBCL cell lines and 100 clinical samples. Inhibition of PI3K by a specific inhibitor, LY294002, induced apoptosis in SUDHL4, SUDHL5, and SUDHL10 (LY-sensitive) cells, whereas SUDHL8 and OCI-LY19 (LY-resistant) cells were refractory to LY294002-induced apoptosis. AKT was phosphorylated in 5 of 5 DLBCL cell lines and inhibition of PI3K caused dephosphorylation/inactivation of constitutively active AKT, FOXO transcription factor, and GSK3 in LY-sensitive cell lines. In addition, there was a decrease in the expression level of inhibitory apoptotic protein, XIAP, in the DLBCL cell lines sensitive to LY294002 after treatment. However, no effect was observed in XIAP protein levels in the resistant DLBCL cell lines following LY294002 treatment. Finally, using immunohistochemistry, p-AKT was detected in 52% of DLBCL tumors tested. Furthermore, in univariate analysis, high p-AKT expression was associated with short survival. In multivariate analysis, this correlation was no longer significant. Altogether, these results suggest that the PI3K/AKT pathway may be a potential target for therapeutic intervention in DLBCL.

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