The Role of microRNAs in the Cisplatin- and Radio-Resistance of Cervical Cancer

Abstract

Cervical cancer is the fourth leading cause of cancer-related death among women worldwide. The chemotherapeutical agent cisplatin, a small platinum-based compound, is considered as the standard therapy for locally advanced cervical cancer or recurrent cancers, sometimes in combination with radiotherapy or other drugs. However, drug resistance and radio-resistance phenomena could reduce the life expectancy of cervical cancer patients. Resistance mechanisms are complex and often involve multiple cellular pathways in which microRNAs (miRNAs) play a fundamental role. MiRNAs are a class of endogenous non-coding small RNAs responsible for post-transcriptional gene regulation. Convincing evidence demonstrates that several deregulated miRNAs are important regulators in the onset of drug and radioresistance in cervical cancer, thus underlying their potential applications in a clinical setting. In this review, we summarized the mechanisms by which miRNAs affect both cisplatin and radioresistance in cervical cancer. We also described the regulatory loops between miRNAs and lncRNAs promoting drug resistance. Besides, we reported evidence for the role of miRNAs in sensitizing cancer cells to cisplatin-based chemotherapy, and provided some suggestions for the development of new combined therapies for cervical cancer.

FOXA1 Leads to Aberrant Expression of SIX4 Affecting Cervical Cancer Cell Growth and Chemoresistance

“…DDP has been considered as the primary chemotherapy for locally advanced CC or recurrent cancers, while it should be taken into consideration that the majority of patients treated for persistent and/or recurrent CC represent previous chemo- or chemoradiation failures [ 13 ]. Thus, for some patients, the establishment of certain molecular mechanisms impairing the response to DDP might have a significant role in improving poor prognosis.…”

Cisplatin for cancer therapy and overcoming chemoresistance

“…Cervical cancer is the fourth common cancer that affects the females for which cisplatin therapy remains the front-line treatment strategy either alone or as an adjuvant or neoadjuvant combined with radiotherapy [194,195]. Cisplatin combined with radiation therapy comprises of the standard treatment for cervical carcinoma but its anti-neoplastic success is obliterated by cisplatin resistance induced by multi-drug resistant transporters and the high activity of the cervical cancer stem cell marker, aldehyde dehydrogenase [196].…”

Cervical cancer heterogeneity: a constant battle against viruses and drugs

“…IPO4-CEBPD-PRKDC axis is associated with chemoresistance by inhibiting PRKDC-driven DNA damage repair [ 127 ]. In addition, an increasing amount of noncoding RNAs have been confirmed and summarized with association to cisplatin resistance [ 128 , 129 ]. For example, LncRNA HNF1A-AS1 could affect resistance by regulating miR-34b and promoting TUFT1 expression [ 130 ].…”