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Figure 8. Cartoon showing ncRNAs and related autophagy targets in cancers affecting women. Schematic representation of miRNAs
and lncRNAs and their involvement in the regulation of the autophagy pathway. →: activation; ⊥: inhibition; ncRNAs: non-coding RNAs;
miRNAs: micro-RNAs; lncRNAs; long non-coding RNAs; ATGs: autophagy-related genes; PTEN: phosphatase and tensin homolog;
UVRAG: UV resistance-associated gene

through the interaction and stabilization of ATG3 mRNA and protein, and this was found to limit ovarian
cancer cell proliferation [129] . On the contrary, the lncRNAs HOTAIR and HULC play a tumor promoter role.
In fact, HOTAIR expression level is higher in serous ovarian and endometrial cancer tissues compared to
normal tissues, making this lncRNA a biomarker associated with poor prognosis [130,131] . HOTAIR positively
correlates with ATG7 expression levels, promoting autophagy-mediated chemoresistance [132] . Consistent
with this finding, in endometrial cancer HOTAIR promoted BECLIN1 expression and up-regulation of
autophagy, and this reduced sensitivity to chemotherapy [133] . The lncRNA HULC promotes tumorigenesis
and is reportedly overexpressed in ovarian cancer, where it was found to inhibit the autophagy machinery
by interacting with ATG7 and thus preventing LC3 maturation [134] . These findings again outline the double-
face role of autophagy in cancer, which is tumor suppressive in the developmental stage, yet it could be
tumor promoting in conferring chemoresistance in the advanced stage.

CONCLUSION AND TRANSLATIONAL PERSPECTIVES
It is well-known the dual role of autophagy in cancer development. On one side, autophagy guarantees
cellular homeostasis and governs cell proliferation, metabolism, invasiveness, and cell death, thus
preventing the onset of malignancies. On the other hand, as pro-survival mechanism, in advanced stages
autophagy supports the survival of cancer cells under harsh conditions (for instance, by promoting a
dormant state) and resistance to cytotoxic therapeutic treatments. Epigenetics plays a pivotal role in
controlling autophagy through the modulation of ATG genes and of their regulators, thus impacting on
cancer development and progression (reviewed in [150] ). This review provides a comprehensive overview of
miRNAs and lncRNAs involved in the development of tumors affecting women through the induction or
inhibition of autophagy process (summarized in Figure 8).

The question raises on how the present knowledge can be translated into the clinics. There are studies
reporting on the diagnostic/prognostic potential of some ncRNAs targeting autophagy. As an example, the
plasma level of miR-16, miR-27a, miR-107, miR-130a, miR-132, and miR-146a was proposed as a signature