Lycorine Downregulates HMGB1 to Inhibit Autophagy and Enhances Bortezomib Activity in Multiple Myeloma

Roy, Mridul; Liang, Long; Xiao, Xiaojuan; Peng, Yuanliang; Luo, Yuhao; Zhou, Weihua; Zhang, Ji; Qiu, Lugui; Zhang, Shuaishuai; Liu, Feng; Ye, Mao; Zhou, Wen; Liu, Jing

doi:10.7150/thno.15584

Cited by 76 publications

(72 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, we speculated that MALAT‐1 expression was involved in the pathophysiological process of MM, but the mechanisms deserve further investigation. It was found that HMGB1 highly expressed in myeloma cell lines than that in the B‐cells [Roy et al, ]. In our study, the expression of HMGB1 was also obviously increased in MM and its change tendency was similar with MALAT‐1.…”

Section: Discussionsupporting

confidence: 73%

“…Additionally, HMGB1 is also closely related to malignant hematological diseases, including lymphoma, myelodysplastic syndrome and MM. HMGB1 was overexpressed in MM and contributed to the growth and proliferation of myeloma cells [Roy et al, ]. The underlying mechanism of HMGB1 in the context of MM has not been clarified previously and needs further research and exploration.…”

mentioning

confidence: 99%

See 1 more Smart Citation

LncRNA MALAT‐1 Elevates HMGB1 to Promote Autophagy Resulting in Inhibition of Tumor Cell Apoptosis in Multiple Myeloma

Gao

et al. 2017

J of Cellular Biochemistry

View full text Add to dashboard Cite

Long non-coding RNAs (lncRNAs) can participate in the pathological process of multiple myeloma (MM) via regulation of specific gene expression and function. This research aimed to study the role of MALAT-1 and the underlying mechanism in MM. In this study, the expression of MALAT-1 and HMGB1 protein in the bone marrow mononuclear cells from MM patients at different stages and in MM cell lines was determined by qRT-PCR and western blot, respectively. The endogenous expression of MALAT-1 and HMGB1 was modulated using lentivirus vectors transfection. CHX chase assay and RIP analyses were performed to explore the interaction between MALAT-1 and HMGB1 in MM. Nude mouse xenograft was made and used for in vivo experiment study. The expression of MALAT-1 and HMGB1 in the bone marrow mononuclear cells from patients with untreated multiple myeloma was dramatically increased, as well as in MM cell lines, KM3 and U266; while MALAT-1 expression and HMGB1 protein level both decreased significantly in complete remission patients. Furthermore, MALAT-1 knockdown facilitated the degradation of HMGB1 at the post-translational level via increase of the ubiquitination of HMGB1 in MM cells. MALAT-1 was shown to promote autophagy in MM through upregulation of HMGB1. In vivo, MALAT-1 knockdown could inhibit tumor growth significantly in tumor-bearing mice and reduced the protein expressions of HMGB1, Beclin-1, and LC3B in tumor tissues. LncRNA MALAT-1 increases the expression level of HMGB1 in MM thereby promotes autophagy resulting in the inhibition of apoptosis. J. Cell. Biochem. 118: 3341-3348, 2017. © 2017 Wiley Periodicals, Inc.

show abstract

Section: Discussionsupporting

confidence: 73%

mentioning

confidence: 99%

LncRNA MALAT‐1 Elevates HMGB1 to Promote Autophagy Resulting in Inhibition of Tumor Cell Apoptosis in Multiple Myeloma

Gao

et al. 2017

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…For instance, several studies have demonstrated that lycorine displays remarkable efficacy in the suppression of tumorigenesis (14,(19)(20)(21)(22)(23). However, the underlying mechanism involved remains poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…Although the targets or mechanisms of lycorine are still undefined, the dominant biological effects and low cytotoxicity of lycorine render it as a potential clinical drug or lead. For instance, it has received much attention as a promising anticancer agent for bladder cancer, cervical cancer, leukemia, prostate cancer, and multiple myeloma (14,(19)(20)(21)(22)(23). However, the defined molecular mechanisms underlying lycorine-regulated suppression of tumorigenesis remain elusive.…”

Section: Introductionmentioning

confidence: 99%

Lycorine Promotes Autophagy and Apoptosis via TCRP1/Akt/mTOR Axis Inactivation in Human Hepatocellular Carcinoma

Qiu

Pang

et al. 2017

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Lycorine is a multifunctional bioactive compound, and it possesses potential anticancer activities. However, little is known about the underlying mechanism. In this research, we have found that lycorine significantly induces the apoptotic and autophagic capacities of hepatocellular carcinoma (HCC) cells in vitro and in vivo. Treatment with specific autophagy inhibitor (3-methyladenine/Bafilomycin A1) or knockdown of LC-3B/Atg5 by siRNA drastically enhances the apoptotic cell death effect by facilitating the switch from autophagy to apoptosis. Molecular validation mechanistically demonstrates that lycorine-induced apoptosis and autophagy in HCC cells is associated with decreased protein levels of tongue cancer resistance-associated protein 1 (TCRP1), and we further find that inhibition of TCRP1 decreases phosphorylation level of Akt and represses Akt/mTOR signaling. Finally, lycorineinduced apoptosis and autophagy suppress the growth of xenograft hepatocellular tumors without remarkable toxicity. Our results elucidate a novel molecular mechanism whereby lycorine promotes apoptosis and autophagy through the TCRP1/Akt/mTOR pathway in HCC. Our results reveal that lycorine might be a potential therapeutic agent for the treatment of HCC.

show abstract

“…Multiple myeloma (MM) is a kind of neoplastic plasma-cell disorder, characterized by the immersion of malignant plasma cells into bone marrow and still incurable [1,2]. The survival terms of patients with MM range from a few weeks to more than 10 years with the five-year survival rate of 40 %.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of Linc00515 Inhibits Multiple Myeloma Autophagy and Chemoresistance by Upregulating miR-140-5p and Downregulating ATG14

Yang

Zhang

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: The purpose of our experiments was to investigate the targeting relationship of linc00515, miR-140-5p and ATG14 and to explore the roles of linc00515, miR-140-5p and ATG14 in autophagy and chemoresistance of melphalan-resistant multiple myeloma cells. Methods: Plasmids that could interfere with the expression of linc00515 and ATG14 were loaded into myeloma cells, which were cultured with melphalan. MTT assay and flow cytometry analysis were utilized to investigate the effect of linc00515, miR-140-5p and ATG14 on the resistance of myeloma cells. QRT-PCR was used to determine the levels of mRNAs. Western blot was utilized to explore the level of ATG14 and autophagy-related proteins. Dual luciferase assay was utilized to explore the targeting relationship between linc00515, miR-140-5p and ATG14. GFP LC3 fluorescence assay was conducted to study the autophagy of cells. Results: The expression of linc00515 and ATG14 were significantly higher in melphalan-resistant myeloma cells. Knockdown of linc00515 and ATG14 led to decreased autophagy and chemoresistance of melphalan-resistant myeloma cells. The forced expression of miR-140-5p suppressed autophagy and chemoresistance of melphalan-resistant myeloma cells. Conclusion: Linc00515 enhanced autophagy and chemoresistance of melphalan-resistant myeloma by directly inhibiting miR-140-5p, which elevated ATG14 level.

show abstract

Lycorine Downregulates HMGB1 to Inhibit Autophagy and Enhances Bortezomib Activity in Multiple Myeloma

Cited by 76 publications

References 66 publications

LncRNA MALAT‐1 Elevates HMGB1 to Promote Autophagy Resulting in Inhibition of Tumor Cell Apoptosis in Multiple Myeloma

LncRNA MALAT‐1 Elevates HMGB1 to Promote Autophagy Resulting in Inhibition of Tumor Cell Apoptosis in Multiple Myeloma

Lycorine Promotes Autophagy and Apoptosis via TCRP1/Akt/mTOR Axis Inactivation in Human Hepatocellular Carcinoma

Knockdown of Linc00515 Inhibits Multiple Myeloma Autophagy and Chemoresistance by Upregulating miR-140-5p and Downregulating ATG14

Contact Info

Product

Resources

About