The Long Non-Coding RNA SAMMSON Is a Regulator of Chemosensitivity and Metabolic Orientation in MCF-7 Doxorubicin-Resistant Breast Cancer Cells

Abstract

Despite improvements in therapeutic strategies for treating breast cancers, tumor relapse and chemoresistance remain major issues in patient outcomes. Indeed, cancer cells display a metabolic plasticity allowing a quick adaptation to the tumoral microenvironment and to cellular stresses induced by chemotherapy. Recently, long non-coding RNA molecules (lncRNAs) have emerged as important regulators of cellular metabolic orientation. In the present study, we addressed the role of the long non-coding RNA molecule (lncRNA) SAMMSON on the metabolic reprogramming and chemoresistance of MCF-7 breast cancer cells resistant to doxorubicin (MCF-7dox). Our results showed an overexpression of SAMMSON in MCF-7dox compared to doxorubicin-sensitive cells (MCF-7). Silencing of SAMMSON expression by siRNA in MCF-7dox cells resulted in a metabolic rewiring with improvement of oxidative metabolism, decreased mitochondrial ROS production, increased mitochondrial replication, transcription and translation and an attenuation of chemoresistance. These results highlight the role of SAMMSON in the metabolic adaptations leading to the development of chemoresistance in breast cancer cells. Thus, targeting SAMMSON expression levels represents a promising therapeutic route to circumvent doxorubicin resistance in breast cancers.

Comprehensive analysis of cuproptosis-related long non-coding RNA signature and personalized therapeutic strategy of breast cancer patients

“…Also of interest, Xing et al proposed that overexpression of SAMMSON could promote the proliferation of TNBC cells by interacting with p53 (30). Furthermore, the study conducted by Charlotte Orre and colleagues revealed the role of SAMMSON in the metabolic adaptations leading to the development of chemoresistance in BC cells (31). In some other studies, SAMMSON was identified as a key lncRNA in the progression of malignant tumors (32)(33)(34).…”

The oncogenic role of SAMMSON lncRNA in tumorigenesis: A comprehensive review with especial focus on melanoma

“…Silencing of SAMMSON inhibits glucose consumption (decrease in the lactate/glucose ratio) while the rate of respiration remarkably increased by modulating complex I activity, and the levels of ROS production decreased. They reveal that after silencing of SMMSON, mitochondrial replication, transcription and translation increased 11 . Xing et al revealed that overexpression of SMMSON increased triple‐negative breast cancer (TNBC) cell proliferation.…”

The role of lncRNAs in the tumor microenvironment and immunotherapy of melanoma

“…In addition, lncRNA-NEAT1 directly targets the expression of many prometastatic genes and tumor microenvironment-related genes (such as STAT3, WNT7A and VEGF-A) by interacting with miR-361, while miR-361 can inhibit tumor proliferation, invasion, stemness and paclitaxel resistance ( 40 ). Moreover, lncRNA-SAMMSON is highly expressed in doxorubicin-resistant cancer cells, resulting in metabolic recombination, reduced production of mitochondrial ROS, increased mitochondrial replication, transcription, and translation, and reduced resistance to chemotherapy ( 41 ).…”