microRNAs in cancer chemoresistance: The sword and the shield.

Cancer is a multifactorial disease and one of the leading causes of mortality worldwide. Cancer cells develop
multiple strategies to reduce drug sensitivity and eventually lead to chemoresistance. Chemoresistance is initiated
either by intrinsic factors or due to the prolonged use of chemotherapeutics as acquired resistance. Further,
chemoresistance is also one of the major reasons behind tumor recurrence and metastasis. Therefore, overcoming
chemoresistance is one of the primary challenges in cancer therapy. Several mechanisms are involved in chemoresistance.
Among them, the key role of ABC transporters and tumor microenvironment have been well
studied. Recently, microRNAs (miRNAs) regulation in tumor development, metastasis, and chemotherapy has got
wider interest due to its role in regulating genes involved in cancer progression and therapy. Noncoding RNAs,
including miRNAs, have been associated with the regulation of tumor-suppressor and tumor-promoter genes.
Further, miRNA can also be used as a reliable diagnostic and prognostic marker to predict the stage and types of
cancer. Recent evidences have revealed that miRNAs regulation also influences the function of drug transporters
and the tumor microenvironment, which affects chemosensitivity to cancer cells. Therefore, miRNAs can be a
promising target to reverse back chemosensitivity in cancer cells. This review comprehensively discusses the
mechanisms involved in cancer chemoresistance and its regulation by miRNAs.